AIM To analyse clinical and long-term oncologic results after laparoscopic complete mesocolic excision(CME) for colonic cancer over a 10-year period.METHODS Consecutive patients who received laparoscopic CME at our ho...AIM To analyse clinical and long-term oncologic results after laparoscopic complete mesocolic excision(CME) for colonic cancer over a 10-year period.METHODS Consecutive patients who received laparoscopic CME at our hospital from 2007 to 2017 were prospectively registered and retrospectively analysed. In total, 341 patients were included with tumour-nodal-metastasis(TNM) stages 0-Ⅲ.RESULTS The mean age of the patients was 71.9 years. The median length of stay was 5 d. The mean lymph node harvest was 17.8. The mortality rate was 1.2%. Fifteen patients were reoperated on for anastomotic leaks. The local recurrence rate was 2.3%. Five-year TTR and cancer-specific survival CSS were 83.1% and 90.3%. The location of the tumour was not a significant variable for survival in unadjusted and adjusted survival analysis. TNM stage and anastomotic leaks were significant variables with respect to survival.CONCLUSION Laparoscopic CME results in acceptable complication rates and long-term oncologic results. It is important to avoid anastomotic leaks because of their negative effect on survival.展开更多
BACKGROUND Synchronous colonic cancer incidence is uncommon,and awareness about this rare condition is improved recently.However,in the presence of acute colonic obstruction,investigation and management of synchronous...BACKGROUND Synchronous colonic cancer incidence is uncommon,and awareness about this rare condition is improved recently.However,in the presence of acute colonic obstruction,investigation and management of synchronous colonic cancer can be difficult and challenging.CASE SUMMARY A patient presented with acute colonic obstruction with impending rupture and complete examination of this patient revealed the presence of three colonic cancers,of which two were completely occluding.CONCLUSION The presence of multiple colonic cancers must be ruled out in order to plan the best management.We present the case with a review of literature and discuss the management of the case.展开更多
<b><span style="font-family:Verdana;">Background:</span></b><span style="font-family:Verdana;"> Cancer colon is one of the most common malignancies.</span><sp...<b><span style="font-family:Verdana;">Background:</span></b><span style="font-family:Verdana;"> Cancer colon is one of the most common malignancies.</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">After colon cancer surgery patients may experience severe pain.</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">Several studies have reported that a significant decrease in postoperative pain with propofol while other studies have showed this effect was not significant. </span><b><span style="font-family:Verdana;">Aim:</span></b><b><span style="font-family:Verdana;"> </span></b><span style="font-family:Verdana;">Our goal was to assess the effect of combined epidural anaesthesia either with propofol</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">or sevoflurane on intraoperative fentanyl consumption and postoperative pain</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">in patients undergoing open surgical resection of colon cancer.</span><span style="font-family:Verdana;"> </span><b><span style="font-family:Verdana;">Patients and Methods:</span></b><span style="font-family:Verdana;"> 48 adult patients suffering from cancer colon scheduled for </span><span style="font-family:Verdana;">open surgical resection randomly allocated either to receive epidural-pro</span><span style="font-family:Verdana;">pofol</span><span style="font-family:Verdana;"> by total intra venous anaesthesia</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">(TIVA)</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">(n</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">=</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">24) or epidural-sevoflu</span><span style="font-family:Verdana;">rane</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">anaesthesia (n</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">=</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">24),</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">intraoperative heart rate and fentanyl consumption and postoperative pain score</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">(verbal analogue scale,</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">0</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">-</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">10) were recorded.</span><span style="font-family:Verdana;"> </span><b><span style="font-family:Verdana;">Results:</span></b><b><span style="font-family:Verdana;"> </span></b><span style="font-family:Verdana;">In our study we found that</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">the intensity of postoperative pain was low in all patients and</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">the propofol based anaesthesia had relatively lower pain scores up to 24</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">hrs postoperatively in comparison to sevoflurane based anaesthesia,</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">intraoperative fentanyl consumption was lower with sevoflurane and heart rate lower with propofol group. </span><b><span style="font-family:Verdana;">Conclusions:</span></b><b><span style="font-family:Verdana;"> </span></b><span style="font-family:Verdana;">we recommend that use of multimodal analgesia decrease postoperative pain in all cancer colon patients undergoing open surgery who anaesthetized with either propofol or sevoflurane.</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">Also use of propofol</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">showed better analgesic outcomes postoperatively.</span>展开更多
Colonic stenting has had a significant positive impact on the management of obstructive left-sided colon cancer(OLCC) in terms of both palliative treatment and bridge-to-surgery(BTS). Notably, many studies have convin...Colonic stenting has had a significant positive impact on the management of obstructive left-sided colon cancer(OLCC) in terms of both palliative treatment and bridge-to-surgery(BTS). Notably, many studies have convincingly demonstrated the effectiveness of stenting as a BTS, resulting in improvements in shortterm outcomes and quality of life, safety, and efficacy in subsequent curative surgery, and increased cost-effectiveness, whereas the safety of chemotherapy after stenting and the long-term outcomes of stenting as a BTS are controversial. Several studies have suggested an increased risk of perforation in patients receiving bevacizumab chemotherapy after colonic stenting. In addition, several pathological analyses have suggested a negative oncological impact of colonic stenting. In contrast, many recent studies have demonstrated that colonic stenting for OLCC does not negatively impact the safety of chemotherapy or long-term oncological outcomes. The updated version of the European Society of Gastrointestinal Endoscopy guidelines released in 2020 included colonic stenting as a BTS for OLCC as a recommended treatment. It should be noted that the experience of endoscopists is involved in determining technical and clinical success rates and possibly oncological outcomes. This review discusses the positive and negative impacts of colonic stenting on OLCC treatment, particularly in terms of oncology.展开更多
Transient receptor potential(TRP)channels are strongly associated with colon cancer development and progression.This study leveraged a multivariate Cox regression model on publicly available datasets to construct a TR...Transient receptor potential(TRP)channels are strongly associated with colon cancer development and progression.This study leveraged a multivariate Cox regression model on publicly available datasets to construct a TRP channels-associated gene signature,with further validation of signature in real world samples from our hospital treated patient samples.Kaplan-Meier(K-M)survival analysis and receiver operating characteristic(ROC)curves were employed to evaluate this gene signature’s predictive accuracy and robustness in both training and testing cohorts,respectively.Additionally,the study utilized the CIBERSORT algorithm and single-sample gene set enrichment analysis to explore the signature’s immune infiltration landscape and underlying functional implications.The support vector machine algorithm was applied to evaluate the signature’s potential in predicting chemotherapy outcomes.The findings unveiled a novel three TRP channels-related gene signature(MCOLN1,TRPM5,and TRPV4)in colon adenocarcinoma(COAD).The ROC and K-M survival curves in the training dataset(AUC=0.761;p=1.58e-05)and testing dataset(AUC=0.699;p=0.004)showed the signature’s robust predictive capability for the overall survival of COAD patients.Analysis of the immune infiltration landscape associated with the signature revealed higher immune infiltration,especially an increased presence of M2 macrophages,in high-risk group patients compared to their low-risk counterparts.High-risk score patients also exhibited potential responsiveness to immune checkpoint inhibitor therapy,evident through increased CD86 and PD-1 expression profiles.Moreover,the TRPM5 gene within the signature was highly expressed in the chemoresistance group(p=0.00095)and associated with poor prognosis(p=0.036)in COAD patients,highlighting its role as a hub gene of chemoresistance.Ultimately,this signature emerged as an independent prognosis factor for COAD patients(p=6.48e-06)and expression of model gene are validated by public data and real-world patients.Overall,this bioinformatics study provides valuable insights into the prognostic implications and potential chemotherapy resistance mechanisms associated with TRPs-related genes in colon cancer.展开更多
BACKGROUND As the primary microtubule organizing center in animal cells,centrosome abnormalities are involved in human colon cancer.AIM To explore the role of centrosome-related genes(CRGs)in colon cancer.METHODS CRGs...BACKGROUND As the primary microtubule organizing center in animal cells,centrosome abnormalities are involved in human colon cancer.AIM To explore the role of centrosome-related genes(CRGs)in colon cancer.METHODS CRGs were collected from public databases.Consensus clustering analysis was performed to separate the Cancer Genome Atlas cohort.Univariate Cox and least absolute shrinkage selection operator regression analyses were performed to identify candidate prognostic CRGs and construct a centrosome-related signature(CRS)to score colon cancer patients.A nomogram was developed to evaluate the CRS risk in colon cancer patients.An integrated bioinformatics analysis was conducted to explore the correlation between the CRS and tumor immune microenvironment and response to immunotherapy,chemotherapy,and targeted therapy.Single-cell transcriptome analysis was conducted to examine the immune cell landscape of core prognostic genes.RESULTS A total of 726 CRGs were collected from public databases.A CRS was constructed,which consisted of the following four genes:TSC1,AXIN2,COPS7A,and MTUS1.Colon cancer patients with a high-risk signature had poor survival.Patients with a high-risk signature exhibited decreased levels of plasma cells and activated memory CD4+T cells.Regarding treatment response,patients with a high-risk signature were resistant to immunotherapy,chemotherapy,and targeted therapy.COPS7A expression was relatively high in endothelial cells and fibroblasts.MTUS1 expression was high in endothelial cells,fibroblasts,and malignant cells.CONCLUSION We constructed a centrosome-related prognostic signature that can accurately predict the prognosis of colon cancer patients,contributing to the development of individualized treatment for colon cancer.展开更多
BACKGROUND Paradoxically,patients with T4N0M0(stage II,no lymph node metastasis)colon cancer have a worse prognosis than those with T2N1-2M0(stage III).However,no previous report has addressed this issue.AIM To screen...BACKGROUND Paradoxically,patients with T4N0M0(stage II,no lymph node metastasis)colon cancer have a worse prognosis than those with T2N1-2M0(stage III).However,no previous report has addressed this issue.AIM To screen prognostic risk factors for T4N0M0 colon cancer and construct a prognostic nomogram model for these patients.METHODS Two hundred patients with T4N0M0 colon cancer were treated at Tianjin Medical University General Hospital between January 2017 and December 2021,of which 112 patients were assigned to the training cohort,and the remaining 88 patients were assigned to the validation cohort.Differences between the training and validation groups were analyzed.The training cohort was subjected to multi-variate analysis to select prognostic risk factors for T4N0M0 colon cancer,followed by the construction of a nomogram model.RESULTS The 3-year overall survival(OS)rates were 86.2%and 74.4%for the training and validation cohorts,respectively.Enterostomy(P=0.000),T stage(P=0.001),right hemicolon(P=0.025),irregular review(P=0.040),and carbohydrate antigen 199(CA199)(P=0.011)were independent risk factors of OS in patients with T4N0M0 colon cancer.A nomogram model with good concordance and accuracy was constructed.CONCLUSION Enterostomy,T stage,right hemicolon,irregular review,and CA199 were independent risk factors for OS in patients with T4N0M0 colon cancer.The nomogram model exhibited good agreement and accuracy.展开更多
BACKGROUND Cyclin-dependent kinase 9(CDK9)expression and autophagy in colorectal cancer(CRC)tissues has not been widely studied.CDK9,a key regulator of transcription,may influence the occurrence and progression of CRC...BACKGROUND Cyclin-dependent kinase 9(CDK9)expression and autophagy in colorectal cancer(CRC)tissues has not been widely studied.CDK9,a key regulator of transcription,may influence the occurrence and progression of CRC.The expression of auto-phagy-related genes BECN1 and drug resistance factor ABCG2 may also play a role in CRC.Under normal physiological conditions,autophagy can inhibit tumorigenesis,but once a tumor forms,autophagy may promote tumor growth.Therefore,understanding the relationship between autophagy and cancer,partic-ularly how autophagy promotes tumor growth after its formation,is a key motivation for this research.AIM To investigate the relationship between CDK9 expression and autophagy in CRC,assess differences in autophagy between left and right colon cancer,and analyze the associations of autophagy-related genes with clinical features and prognosis.METHODS We collected tumor tissues and paracarcinoma tissues from colon cancer patients with liver metastasis to observe the level of autophagy in tissues with high levels of CDK9 and low levels of CDK9.We also collected primary tissue from left and right colon cancer patients with liver metastasis to compare the autophagy levels and the expression of BECN1 and ABCG2 in the tumor and paracarcinoma tissues.RESULTS The incidence of autophagy and the expression of BECN1 and ABCG2 were different in left and right colon cancer,and autophagy might be involved in the occurrence of chemotherapy resistance.Further analysis of the rela-tionship between the expression of autophagy-related genes CDK9,ABCG2,and BECN1 and the clinical features and prognosis of colorectal cancer showed that the high expression of CDK9 indicated a poor prognosis in colorectal cancer.CONCLUSION This study laid the foundation for further research on the combination of CDK9 inhibitors and autophagy inhibitors in the treatment of patients with CRC.展开更多
BACKGROUND The role of Sm-like 5(LSM5)in colon cancer has not been determined.In this study,we investigated the role of LSM5 in progression of colon cancer and the potential underlying mechanism involved.AIM To determ...BACKGROUND The role of Sm-like 5(LSM5)in colon cancer has not been determined.In this study,we investigated the role of LSM5 in progression of colon cancer and the potential underlying mechanism involved.AIM To determine the role of LSM5 in the progression of colon cancer and the potential underlying mechanism involved.METHODS The Gene Expression Profiling Interactive Analysis database and the Human Protein Atlas website were used for LSM5 expression analysis and prognosis analysis.Real-time quantitative polymerase chain reaction and Western blotting were utilized to detect the expression of mRNAs and proteins.A lentivirus targeting LSM5 was constructed and transfected into colon cancer cells to silence LSM5 expression.Proliferation and apoptosis assays were also conducted to evaluate the growth of the colon cancer cells.Human GeneChip assay and bioinformatics analysis were performed to identify the potential underlying mechanism of LSM5 in colon cancer.RESULTS LSM5 was highly expressed in tumor tissue and colon cancer cells.A high expression level of LSM5 was related to poor prognosis in patients with colon cancer.Knockdown of LSM5 suppressed proliferation and promoted apoptosis in colon cancer cells.Silencing of LSM5 also facilitates the expression of p53,cyclin-dependent kinase inhibitor 1A(CDKN1A)and tumor necrosis factor receptor superfamily 10B(TNFRSF10B).The inhibitory effect of LSM5 knockdown on the growth of colon cancer cells was associated with the upregulation of p53,CDKN1A and TNFRSF10B.CONCLUSION LSM5 knockdown inhibited the proliferation and facilitated the apoptosis of colon cancer cells by upregulating p53,CDKN1A and TNFRSF10B.展开更多
The role of lncRNA KCNQ1 opposite strand/antisense transcript 1(KCNQ1OT1)in colon cancer involves various tumorigenic processes and has been studed widely.However,the mechanism by which it promotes colon cancer remain...The role of lncRNA KCNQ1 opposite strand/antisense transcript 1(KCNQ1OT1)in colon cancer involves various tumorigenic processes and has been studed widely.However,the mechanism by which it promotes colon cancer remains unclear.Retrovirnl vector pSEB61 was retroftted in established HCT116 siKCN and SW480-siKCN cells to silence KCNQ1 OT1.Cellular proliferation was measured using CCK8 assay,and flow cytometry(FCM)detected cell cydle changes.RNA sequencing(RNA Seq)analysis showed differentially expressed genes(DEGs).Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses were carried out to analyze enriched functions and signaling pathways.RT-qPCR,immunofluorescence,and western blotting were carried out to validate downstream gene expressions.The effects of tumorigenesis were evaluated in BALB/c nude mice by tumor xenografts.Our data revealed that the silencing of KONQ1OT1 in HCT116 and SW480 cells slowed cell growth and decreased the number of cells in the G2/M phase.RNA-Seq analysis showed the data of DEGs enriched in various GO and KEGG pathways such as DNA replication and cell cyde.RT qPCR,immunofluorescence,and western blotting confirmed downstream CCNE2 and PCNA gene expressions.HCT116 siKCN cells signifcantly suppressed tumorigenesis in BALB/c nude mice.Our study suggests that lncRNA KCNQ1OT1 may provide a promising therapeutic strategy for colon cancer.展开更多
BACKGROUND Limited knowledge exists regarding the casual associations linking blood metabolites and the risk of developing colorectal cancer.AIM To investigate causal associations between blood metabolites and colon c...BACKGROUND Limited knowledge exists regarding the casual associations linking blood metabolites and the risk of developing colorectal cancer.AIM To investigate causal associations between blood metabolites and colon cancer.METHODS The study utilized a two-sample Mendelian randomization(MR)analysis to investigate the causal impact of 486 blood metabolites on colorectal cancer.The primary method of analysis used was the inverse variance weighted model.To further validate the results several sensitivity analyses were performed,including Cochran's Q test,MR-Egger intercept test,and MR robust adjusted profile score.These additional analyses were conducted to ensure the reliability and robustness of the findings.RESULTS After rigorous selection for genetic variation,486 blood metabolites were included in the MR analysis.We found Mannose[odds ratio(OR)=2.09(1.10-3.97),P=0.024],N-acetylglycine[OR=3.14(1.78-5.53),P=7.54×10^(-8)],X-11593-O-methylascorbate[OR=1.68(1.04-2.72),P=0.034],1-arachidonoylglycerophosphocholine[OR=4.23(2.51-7.12),P=6.35×10^(-8)]and 1-arachidonoylglycerophosphoethanolamine 4[OR=3.99(1.17-13.54),P=0.027]were positively causally associated with colorectal cancer,and we also found a negative causal relationship between Tyrosine[OR=0.08(0.01-0.63),P=0.014],Urate[OR=0.25(0.10-0.62),P=0.003],N-acetylglycine[0.73(0.54-0.98),P=0.033],X-12092[OR=0.89(0.81-0.99),P=0.028],Succinylcarnitine[OR=0.48(0.27-0.84),P=0.09]with colorectal cancer.A series of sensitivity analyses were performed to confirm the rigidity of the results.CONCLUSION This study showed a causal relationship between 10 blood metabolites and colorectal cancer,of which 5 blood metabolites were found to be causal for the development of colorectal cancer and were confirmed as risk factors.The other five blood metabolites are protective factors.展开更多
BACKGROUND Colorectal cancer has a low 5-year survival rate and high mortality.Humanβ-defensin-1(hBD-1)may play an integral function in the innate immune system,contributing to the recognition and destruction of canc...BACKGROUND Colorectal cancer has a low 5-year survival rate and high mortality.Humanβ-defensin-1(hBD-1)may play an integral function in the innate immune system,contributing to the recognition and destruction of cancer cells.Long non-coding RNAs(lncRNAs)are involved in the process of cell differentiation and growth.AIM To investigate the effect of hBD-1 on the mammalian target of rapamycin(mTOR)pathway and autophagy in human colon cancer SW620 cells.METHODS CCK8 assay was utilized for the detection of cell proliferation and determination of the optimal drug concentration.Colony formation assay was employed to assess the effect of hBD-1 on SW620 cell proliferation.Bioinformatics was used to screen potentially biologically significant lncRNAs related to the mTOR pathway.Additionally,p-mTOR(Ser2448),Beclin1,and LC3II/I expression levels in SW620 cells were assessed through Western blot analysis.RESULTS hBD-1 inhibited the proliferative ability of SW620 cells,as evidenced by the reduction in the colony formation capacity of SW620 cells upon exposure to hBD-1.hBD-1 decreased the expression of p-mTOR(Ser2448)protein and increased the expression of Beclin1 and LC3II/I protein.Furthermore,bioinformatics analysis identified seven lncRNAs(2 upregulated and 5 downregulated)related to the mTOR pathway.The lncRNA TCONS_00014506 was ultimately selected.Following the inhibition of the lncRNA TCONS_00014506,exposure to hBD-1 inhibited p-mTOR(Ser2448)and promoted Beclin1 and LC3II/I protein expression.CONCLUSION hBD-1 inhibits the mTOR pathway and promotes autophagy by upregulating the expression of the lncRNA TCONS_00014506 in SW620 cells.展开更多
BACKGROUND Colon cancer(CC)occurrence and progression are considerably influenced by the tumor microenvironment.However,the exact underlying regulatory mechanisms remain unclear.AIM To investigate immune infiltration-...BACKGROUND Colon cancer(CC)occurrence and progression are considerably influenced by the tumor microenvironment.However,the exact underlying regulatory mechanisms remain unclear.AIM To investigate immune infiltration-related differentially expressed genes(DEGs)in CC and specifically explored the role and potential molecular mechanisms of complement factor I(CFI).METHODS Immune infiltration-associated DEGs were screened for CC using bioinformatics.Quantitative reverse transcription polymerase chain reaction was used to examine hub DEGs expression in the CC cell lines.Stable CFI-knockdown HT29 and HCT116 cell lines were constructed,and the diverse roles of CFI in vitro were assessed using CCK-8,5-ethynyl-2’-deoxyuridine,wound healing,and transwell assays.Hematoxylin and eosin staining and immunohistochemistry staining were employed to evaluate the influence of CFI on the tumorigenesis of CC xenograft models constructed using BALB/c male nude mice.Key proteins associated with glycolysis and the Wnt pathway were measured using western blotting.RESULTS Six key immune infiltration-related DEGs were screened,among which the expression of CFI,complement factor B,lymphoid enhancer binding factor 1,and SRY-related high-mobility-group box 4 was upregulated,whereas that of fatty acid-binding protein 1,and bone morphogenic protein-2 was downregulated.Furthermore,CFI could be used as a diagnostic biomarker for CC.Functionally,CFI silencing inhibited CC cell proliferation,migration,invasion,and tumor growth.Mechanistically,CFI knockdown downregulated the expression of key glycolysis-related proteins(glucose transporter type 1,hexokinase 2,lactate dehydrogenase A,and pyruvate kinase M2)and the Wnt pathway-related proteins(β-catenin and c-Myc).Further investigation indicated that CFI knockdown inhibited glycolysis in CC by blocking the Wnt/β-catenin/c-Myc pathway.CONCLUSION The findings of the present study demonstrate that CFI plays a crucial role in CC development by influencing glycolysis and the Wnt/β-catenin/c-Myc pathway,indicating that it could serve as a promising target for therapeutic intervention in CC.展开更多
In this editorial we comment on the manuscript,describing management and surveillance strategies in synchronous and metachronous,gastric and colon cancers.Synchronous or metachronous primary malignancies at different ...In this editorial we comment on the manuscript,describing management and surveillance strategies in synchronous and metachronous,gastric and colon cancers.Synchronous or metachronous primary malignancies at different sites of the gastrointestinal tract pose a unique diagnostic and therapeutic challenge.Multidisciplinary services and strategies are required for the management of multiple site primary malignancies,to provide the best oncological outcomes.Although this study highlights the dual cancers in 76 sporadic cases,the authors excluded 55 patients due to combination of factors which includes;incomplete clinical data,genetic syndrome,gastric stump cancers.In addition,the authors did not elaborate if any patients presented with signet ring cell morphology,E-cadherin mutations or presence of inflammatory bowel disease.Genetic and mutational errors and epithelial field defects from chronic inflammatory diseases of the gastrointestinal tract are important when considering synchronous gastric and colonic cancers.We will briefly discuss these in this editorial.展开更多
BACKGROUND Heterogeneous ribonucleoprotein A1(hnRNPA1)has been reported to enhance the Warburg effect and promote colon cancer(CC)cell proliferation,but the role and mechanism of the miR-490-3p/hnRNPA1-b/PKM2 axis in ...BACKGROUND Heterogeneous ribonucleoprotein A1(hnRNPA1)has been reported to enhance the Warburg effect and promote colon cancer(CC)cell proliferation,but the role and mechanism of the miR-490-3p/hnRNPA1-b/PKM2 axis in CC have not yet been elucidated.AIM To investigate the role and mechanism of a novel miR-490-3p/hnRNPA1-b/PKM2 axis in enhancing the Warburg effect and promoting CC cell proliferation through the PI3K/AKT pathway.METHODS Paraffin-embedded pathological sections from 220 CC patients were collected and subjected to immunohistochemical analysis to determine the expression of hnRNPA1-b.The relationship between the expression values and the clinicopathological features of the patients was investigated.Differences in mRNA expression were analyzed using quantitative real-time polymerase chain reaction,while differences in protein expression were analyzed using western blot.Cell proliferation was evaluated using the cell counting kit-8 and 5-ethynyl-2’-deoxyuridine assays,and cell cycle and apoptosis were detected using flow cytometric assays.The targeted binding of miR-490-3p to hnRNPA1-b was validated using a dual luciferase reporter assay.The Warburg effect was evaluated by glucose uptake and lactic acid production assays.RESULTS The expression of hnRNPA1-b was significantly increased in CC tissues and cells compared to normal controls(P<0.05).Immunohistochemical results demonstrated significant variations in the expression of the hnRNPA1-b antigen in different stages of CC,including stage I,II-III,and IV.Furthermore,the clinicopathologic characterization revealed a significant correlation between hnRNPA1-b expression and clinical stage as well as T classification.HnRNPA1-b was found to enhance the Warburg effect through the PI3K/AKT pathway,thereby promoting proliferation of HCT116 and SW620 cells.However,the proliferation of HCT116 and SW620 cells was inhibited when miR-490-3p targeted and bound to hnRNPA1-b,effectively blocking the Warburg effect.CONCLUSION These findings suggest that the novel miR-490-3p/hnRNPA1-b/PKM2 axis could provide a new strategy for the diagnosis and treatment of CC.展开更多
In this editorial,I commented on the paper by Lin et al,published in this issue of the World Journal of Gastrointestinal Oncology.The work aimed at analysing the clinicopathologic characteristics and prognosis of sync...In this editorial,I commented on the paper by Lin et al,published in this issue of the World Journal of Gastrointestinal Oncology.The work aimed at analysing the clinicopathologic characteristics and prognosis of synchronous and metachronous cancers in patients with dual primary gastric and colorectal cancer(CRC).The authors concluded the necessity for regular surveillance for metachronous cancer during postoperative follow-up and reported the prognosis is influenced by the gastric cancer(GC)stage rather than the CRC stage.Although surveillance was recommended in the conclusion,the authors did not explore this area in their study and did not include tests used for such surveillance.This editorial focuses on the most characterized gastrointestinal cancer susceptibility syndromes concerning dual gastric and CRCs.These include hereditary diffuse GC,familial adenomatous polyposis,hereditary nonpolyposis colon cancer,Lynch syndrome,and three major hamartomatous polyposis syndromes associated with CRC and GC,namely Peutz-Jeghers syndrome,juvenile polyposis syndrome,and PTEN hamartoma syndrome.Careful assessment of these syndromes/conditions,including inheritance,risk of gastric and colorectal or other cancer development,genetic mutations and recommended genetic investigations,is crucial for optimum management of these patients.展开更多
BACKGROUND Colon cancer is acknowledged as one of the most common malignancies worldwide,ranking third in United States regarding incidence and mortality.Notably,approximately 40%of colon cancer cases harbor oncogenic...BACKGROUND Colon cancer is acknowledged as one of the most common malignancies worldwide,ranking third in United States regarding incidence and mortality.Notably,approximately 40%of colon cancer cases harbor oncogenic KRAS mutations,resulting in the continuous activation of epidermal growth factor receptor signaling.AIM To investigate the key pathogenic genes in KRAS mutant colon cancer holds considerable importance.METHODS Weighted gene co-expression network analysis,in combination with additional bioinformatics analysis,were conducted to screen the key factors driving the progression of KRAS mutant colon cancer.Meanwhile,various in vitro experiments were also conducted to explore the biological function of transglutaminase 2(TGM2).RESULTS Integrated analysis demonstrated that TGM2 acted as an independent prognostic factor for progression-free survival.Immunohistochemical analysis on tissue microarrays revealed that TGM2 was associated with an elevated probability of perineural invasion in patients with KRAS mutant colon cancer.Additionally,biological roles of the key gene TGM2 was also assessed,suggesting that the downregulation of TGM2 attenuated the proliferation,invasion,and migration of the KRAS mutant colon cancer cell line.CONCLUSION This study underscores the potential significance of TGM2 in the progression of KRAS mutant colon cancer.This insight not only offers a theoretical foundation for therapeutic approaches but also highlights the need for additional clinical trials and fundamental research to support our preliminary findings.展开更多
BACKGROUND Colon cancer(CC)has a high incidence rate.Radical resection is the main treatment method for CC;however,liver metastasis(LM)often occurs post-surgery.The liver contains both innate and adaptive immune cells...BACKGROUND Colon cancer(CC)has a high incidence rate.Radical resection is the main treatment method for CC;however,liver metastasis(LM)often occurs post-surgery.The liver contains both innate and adaptive immune cells that monitor and remove abnormal cells and pathogens.Before LM,tumor cells secrete cytokines and exosomes to adjust the immune microenvironment of the liver,thus forming an inhibitory immune microenvironment for colonization by circulating tumor cells.This indicates that the immune state of patients with CC plays a crucial role in the occurrence and progression of LM.AIM To observe and analyze the relationship between immune status and expression of tumor factors in patients with LM of CC,and to provide a scientific interven-tion method for promoting the patient prognosis.METHODS A retrospective analysis was performed.The baseline data of 100 patients with CC and 100 patients with CC who suffered from postoperative LM and were admitted to our hospital from May 2021 to May 2023 were included in the non-occurrence and occurrence groups,respectively.The immune status of the pa-tients and the expression of tumor factor-related indicators in the two groups were compared,and the predictive value of the indicators for postoperative LM in patients with CC was analyzed.RESULTS Compared with the non-occurrence group,the expression of serum carcinoem-bryonic antigen(CEA),CA19-9,CA242,CA72-4 and CA50 in patients in the occurrence group were significantly higher,while the expression of CD3+,CD4+,CD8+,natural killer(NK)and CD4+/CD25 in patients in the occurrence group were significantly lower(P<0.05).No significant difference was observed in other baseline data between groups(P>0.05).Multivariate logistic regression model analysis revealed that the expressions of CEA,CA19-9,CA242,CA72-4,CA50,CD3+,CD4+,CD8+,NK,and CD4+/CD25 were associated with the LM in patients with CC.High expressions of serum CEA,CA19-9,CA242,CA72-4 and CA50,and low expressions of CD3+,CD4+,CD8+,NK,and CD4+/CD25 in patients with CC were risk factors for LM(OR>1,P<0.05).The receiver operating characteristic curve showed that the area under curve for CEA,CA19-9,CA242,CA72-4,CA50,CD3+,CD4+,CD8+,NK,and CD4+/CD25 in the prediction of LM in patients with CC were all>0.80,with a high predictive value.CONCLUSION The expression of tumor factors and immune state-related indices in patients with CC is closely associated with the occurrence of LM.展开更多
BACKGROUND Although intracorporeal anastomosis(IA)for colon cancer requires longer operative time than extracorporeal anastomosis(EA),its short-term postoperative results,such as early recovery of bowel movement,have ...BACKGROUND Although intracorporeal anastomosis(IA)for colon cancer requires longer operative time than extracorporeal anastomosis(EA),its short-term postoperative results,such as early recovery of bowel movement,have been reported to be equal or better.As IA requires opening the intestinal tract in the abdominal cavity under pneumoperitoneum,there are concerns about intraperitoneal bacterial infection and recurrence of peritoneal dissemination due to the spread of bacteria and tumor cells.However,intraperitoneal bacterial contamination and medium-term oncological outcomes have not been clarified.abdominal cavity in IA.METHODS Of 127 patients who underwent laparoscopic colon resection for colon cancer from April 2015 to December 2020,75 underwent EA(EA group),and 52 underwent IA(IA group).After propensity score matching,the primary endpoint was 3-year disease-free survival rates,and secondary endpoints were 3-year overall survival rates,type of recurrence,surgical site infection(SSI)incidence,number of days on antibiotics,and postoperative biological responses.RESULTS Three-year disease-free survival rates did not significantly differ between the IA and EA groups(87.2%and 82.7%,respectively,P=0.4473).The 3-year overall survival rates also did not significantly differ between the IA and EA groups(94.7%and 94.7%,respectively;P=0.9891).There was no difference in the type of recurrence between the two groups.In addition,there were no significant differences in SSI incidence or the number of days on antibiotics;however,postoperative biological responses,such as the white blood cell count(10200 vs 8650/mm^(3),P=0.0068),C-reactive protein(6.8 vs 4.5 mg/dL,P=0.0011),and body temperature(37.7 vs 37.5℃,P=0.0079),were significantly higher in the IA group.CONCLUSION IA is an anastomotic technique that should be widely performed because its risk of intraperitoneal bacterial contamination and medium-term oncological outcomes are comparable to those of EA.展开更多
BACKGROUND Colon cancer is one of the most common malignant tumors of the digestive system.Liver metastasis after colon cancer surgery is the primary cause of death in patients with colon cancer.AIM To construct a nov...BACKGROUND Colon cancer is one of the most common malignant tumors of the digestive system.Liver metastasis after colon cancer surgery is the primary cause of death in patients with colon cancer.AIM To construct a novel nomogram model including various factors to predict liver metastasis after colon cancer surgery.METHODS We retrospectively analyzed 242 patients with colon cancer who were admitted and underwent radical resection for colon cancer in Zhejiang Provincial People’s Hospital from December 2019 to December 2022.Patients were divided into liver metastasis and non-liver metastasis groups.Sex,age,and other general and clinicopathological data(preoperative blood routine and biochemical test indexes)were compared.The risk factors for liver metastasis were analyzed using singlefactor and multifactorial logistic regression.A predictive model was then constructed and evaluated for efficacy.RESULTS Systemic inflammatory index(SII),C-reactive protein/albumin ratio(CAR),red blood cell distribution width(RDW),alanine aminotransferase,preoperative carcinoembryonic antigen level,and lymphatic metastasis were different between groups(P<0.05).SII,CAR,and RDW were risk factors for liver metastasis after colon cancer surgery(P<0.05).The area under the curve was 0.93 for the column-line diagram prediction model constructed based on these risk factors to distinguish whether liver metastasis occurred postoperatively.The actual curve of the column-line diagram predicting the risk of postoperative liver metastasis was close to the ideal curve,with good agreement.The prediction model curves in the decision curve analysis showed higher net benefits for a larger threshold range than those in extreme cases,indicating that the model is safer.CONCLUSION Liver metastases after colorectal cancer surgery could be well predicted by a nomogram based on the SII,CAR,and RDW.展开更多
文摘AIM To analyse clinical and long-term oncologic results after laparoscopic complete mesocolic excision(CME) for colonic cancer over a 10-year period.METHODS Consecutive patients who received laparoscopic CME at our hospital from 2007 to 2017 were prospectively registered and retrospectively analysed. In total, 341 patients were included with tumour-nodal-metastasis(TNM) stages 0-Ⅲ.RESULTS The mean age of the patients was 71.9 years. The median length of stay was 5 d. The mean lymph node harvest was 17.8. The mortality rate was 1.2%. Fifteen patients were reoperated on for anastomotic leaks. The local recurrence rate was 2.3%. Five-year TTR and cancer-specific survival CSS were 83.1% and 90.3%. The location of the tumour was not a significant variable for survival in unadjusted and adjusted survival analysis. TNM stage and anastomotic leaks were significant variables with respect to survival.CONCLUSION Laparoscopic CME results in acceptable complication rates and long-term oncologic results. It is important to avoid anastomotic leaks because of their negative effect on survival.
文摘BACKGROUND Synchronous colonic cancer incidence is uncommon,and awareness about this rare condition is improved recently.However,in the presence of acute colonic obstruction,investigation and management of synchronous colonic cancer can be difficult and challenging.CASE SUMMARY A patient presented with acute colonic obstruction with impending rupture and complete examination of this patient revealed the presence of three colonic cancers,of which two were completely occluding.CONCLUSION The presence of multiple colonic cancers must be ruled out in order to plan the best management.We present the case with a review of literature and discuss the management of the case.
文摘<b><span style="font-family:Verdana;">Background:</span></b><span style="font-family:Verdana;"> Cancer colon is one of the most common malignancies.</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">After colon cancer surgery patients may experience severe pain.</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">Several studies have reported that a significant decrease in postoperative pain with propofol while other studies have showed this effect was not significant. </span><b><span style="font-family:Verdana;">Aim:</span></b><b><span style="font-family:Verdana;"> </span></b><span style="font-family:Verdana;">Our goal was to assess the effect of combined epidural anaesthesia either with propofol</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">or sevoflurane on intraoperative fentanyl consumption and postoperative pain</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">in patients undergoing open surgical resection of colon cancer.</span><span style="font-family:Verdana;"> </span><b><span style="font-family:Verdana;">Patients and Methods:</span></b><span style="font-family:Verdana;"> 48 adult patients suffering from cancer colon scheduled for </span><span style="font-family:Verdana;">open surgical resection randomly allocated either to receive epidural-pro</span><span style="font-family:Verdana;">pofol</span><span style="font-family:Verdana;"> by total intra venous anaesthesia</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">(TIVA)</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">(n</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">=</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">24) or epidural-sevoflu</span><span style="font-family:Verdana;">rane</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">anaesthesia (n</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">=</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">24),</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">intraoperative heart rate and fentanyl consumption and postoperative pain score</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">(verbal analogue scale,</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">0</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">-</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">10) were recorded.</span><span style="font-family:Verdana;"> </span><b><span style="font-family:Verdana;">Results:</span></b><b><span style="font-family:Verdana;"> </span></b><span style="font-family:Verdana;">In our study we found that</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">the intensity of postoperative pain was low in all patients and</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">the propofol based anaesthesia had relatively lower pain scores up to 24</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">hrs postoperatively in comparison to sevoflurane based anaesthesia,</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">intraoperative fentanyl consumption was lower with sevoflurane and heart rate lower with propofol group. </span><b><span style="font-family:Verdana;">Conclusions:</span></b><b><span style="font-family:Verdana;"> </span></b><span style="font-family:Verdana;">we recommend that use of multimodal analgesia decrease postoperative pain in all cancer colon patients undergoing open surgery who anaesthetized with either propofol or sevoflurane.</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">Also use of propofol</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">showed better analgesic outcomes postoperatively.</span>
文摘Colonic stenting has had a significant positive impact on the management of obstructive left-sided colon cancer(OLCC) in terms of both palliative treatment and bridge-to-surgery(BTS). Notably, many studies have convincingly demonstrated the effectiveness of stenting as a BTS, resulting in improvements in shortterm outcomes and quality of life, safety, and efficacy in subsequent curative surgery, and increased cost-effectiveness, whereas the safety of chemotherapy after stenting and the long-term outcomes of stenting as a BTS are controversial. Several studies have suggested an increased risk of perforation in patients receiving bevacizumab chemotherapy after colonic stenting. In addition, several pathological analyses have suggested a negative oncological impact of colonic stenting. In contrast, many recent studies have demonstrated that colonic stenting for OLCC does not negatively impact the safety of chemotherapy or long-term oncological outcomes. The updated version of the European Society of Gastrointestinal Endoscopy guidelines released in 2020 included colonic stenting as a BTS for OLCC as a recommended treatment. It should be noted that the experience of endoscopists is involved in determining technical and clinical success rates and possibly oncological outcomes. This review discusses the positive and negative impacts of colonic stenting on OLCC treatment, particularly in terms of oncology.
基金the Ethics Committee of University Magdeburg(Ethical code:33/0119.03.2001).
文摘Transient receptor potential(TRP)channels are strongly associated with colon cancer development and progression.This study leveraged a multivariate Cox regression model on publicly available datasets to construct a TRP channels-associated gene signature,with further validation of signature in real world samples from our hospital treated patient samples.Kaplan-Meier(K-M)survival analysis and receiver operating characteristic(ROC)curves were employed to evaluate this gene signature’s predictive accuracy and robustness in both training and testing cohorts,respectively.Additionally,the study utilized the CIBERSORT algorithm and single-sample gene set enrichment analysis to explore the signature’s immune infiltration landscape and underlying functional implications.The support vector machine algorithm was applied to evaluate the signature’s potential in predicting chemotherapy outcomes.The findings unveiled a novel three TRP channels-related gene signature(MCOLN1,TRPM5,and TRPV4)in colon adenocarcinoma(COAD).The ROC and K-M survival curves in the training dataset(AUC=0.761;p=1.58e-05)and testing dataset(AUC=0.699;p=0.004)showed the signature’s robust predictive capability for the overall survival of COAD patients.Analysis of the immune infiltration landscape associated with the signature revealed higher immune infiltration,especially an increased presence of M2 macrophages,in high-risk group patients compared to their low-risk counterparts.High-risk score patients also exhibited potential responsiveness to immune checkpoint inhibitor therapy,evident through increased CD86 and PD-1 expression profiles.Moreover,the TRPM5 gene within the signature was highly expressed in the chemoresistance group(p=0.00095)and associated with poor prognosis(p=0.036)in COAD patients,highlighting its role as a hub gene of chemoresistance.Ultimately,this signature emerged as an independent prognosis factor for COAD patients(p=6.48e-06)and expression of model gene are validated by public data and real-world patients.Overall,this bioinformatics study provides valuable insights into the prognostic implications and potential chemotherapy resistance mechanisms associated with TRPs-related genes in colon cancer.
基金Supported by Heilongjiang Postdoctoral Fund,No.LBH-Z18214Haiyan Foundation of Harbin Medical University Cancer Hospital,No.JJQN2014-06Foundation of Health Commission of Heilongjiang Province,No.2016-096.
文摘BACKGROUND As the primary microtubule organizing center in animal cells,centrosome abnormalities are involved in human colon cancer.AIM To explore the role of centrosome-related genes(CRGs)in colon cancer.METHODS CRGs were collected from public databases.Consensus clustering analysis was performed to separate the Cancer Genome Atlas cohort.Univariate Cox and least absolute shrinkage selection operator regression analyses were performed to identify candidate prognostic CRGs and construct a centrosome-related signature(CRS)to score colon cancer patients.A nomogram was developed to evaluate the CRS risk in colon cancer patients.An integrated bioinformatics analysis was conducted to explore the correlation between the CRS and tumor immune microenvironment and response to immunotherapy,chemotherapy,and targeted therapy.Single-cell transcriptome analysis was conducted to examine the immune cell landscape of core prognostic genes.RESULTS A total of 726 CRGs were collected from public databases.A CRS was constructed,which consisted of the following four genes:TSC1,AXIN2,COPS7A,and MTUS1.Colon cancer patients with a high-risk signature had poor survival.Patients with a high-risk signature exhibited decreased levels of plasma cells and activated memory CD4+T cells.Regarding treatment response,patients with a high-risk signature were resistant to immunotherapy,chemotherapy,and targeted therapy.COPS7A expression was relatively high in endothelial cells and fibroblasts.MTUS1 expression was high in endothelial cells,fibroblasts,and malignant cells.CONCLUSION We constructed a centrosome-related prognostic signature that can accurately predict the prognosis of colon cancer patients,contributing to the development of individualized treatment for colon cancer.
基金Supported by Health Science and Technology Project of Tianjin Health Commission,No.ZC20190Tianjin Key Medical Discipline(Specialty)Construction Project,No.TJYXZDXK-005ATianjin Medical University Clinical Research Fund,No.22ZYYLCCG04.
文摘BACKGROUND Paradoxically,patients with T4N0M0(stage II,no lymph node metastasis)colon cancer have a worse prognosis than those with T2N1-2M0(stage III).However,no previous report has addressed this issue.AIM To screen prognostic risk factors for T4N0M0 colon cancer and construct a prognostic nomogram model for these patients.METHODS Two hundred patients with T4N0M0 colon cancer were treated at Tianjin Medical University General Hospital between January 2017 and December 2021,of which 112 patients were assigned to the training cohort,and the remaining 88 patients were assigned to the validation cohort.Differences between the training and validation groups were analyzed.The training cohort was subjected to multi-variate analysis to select prognostic risk factors for T4N0M0 colon cancer,followed by the construction of a nomogram model.RESULTS The 3-year overall survival(OS)rates were 86.2%and 74.4%for the training and validation cohorts,respectively.Enterostomy(P=0.000),T stage(P=0.001),right hemicolon(P=0.025),irregular review(P=0.040),and carbohydrate antigen 199(CA199)(P=0.011)were independent risk factors of OS in patients with T4N0M0 colon cancer.A nomogram model with good concordance and accuracy was constructed.CONCLUSION Enterostomy,T stage,right hemicolon,irregular review,and CA199 were independent risk factors for OS in patients with T4N0M0 colon cancer.The nomogram model exhibited good agreement and accuracy.
基金the Science and Technology Development Fund of Tianjin Education Commission for Higher Education,No.2020KJ133Tianjin Key Medical Discipline(Specialty)Construction Project,No.TJYXZDXK-009A.
文摘BACKGROUND Cyclin-dependent kinase 9(CDK9)expression and autophagy in colorectal cancer(CRC)tissues has not been widely studied.CDK9,a key regulator of transcription,may influence the occurrence and progression of CRC.The expression of auto-phagy-related genes BECN1 and drug resistance factor ABCG2 may also play a role in CRC.Under normal physiological conditions,autophagy can inhibit tumorigenesis,but once a tumor forms,autophagy may promote tumor growth.Therefore,understanding the relationship between autophagy and cancer,partic-ularly how autophagy promotes tumor growth after its formation,is a key motivation for this research.AIM To investigate the relationship between CDK9 expression and autophagy in CRC,assess differences in autophagy between left and right colon cancer,and analyze the associations of autophagy-related genes with clinical features and prognosis.METHODS We collected tumor tissues and paracarcinoma tissues from colon cancer patients with liver metastasis to observe the level of autophagy in tissues with high levels of CDK9 and low levels of CDK9.We also collected primary tissue from left and right colon cancer patients with liver metastasis to compare the autophagy levels and the expression of BECN1 and ABCG2 in the tumor and paracarcinoma tissues.RESULTS The incidence of autophagy and the expression of BECN1 and ABCG2 were different in left and right colon cancer,and autophagy might be involved in the occurrence of chemotherapy resistance.Further analysis of the rela-tionship between the expression of autophagy-related genes CDK9,ABCG2,and BECN1 and the clinical features and prognosis of colorectal cancer showed that the high expression of CDK9 indicated a poor prognosis in colorectal cancer.CONCLUSION This study laid the foundation for further research on the combination of CDK9 inhibitors and autophagy inhibitors in the treatment of patients with CRC.
基金Supported by Natural Science Basic Research Program of Shaanxi Province,No.2021JM-256.
文摘BACKGROUND The role of Sm-like 5(LSM5)in colon cancer has not been determined.In this study,we investigated the role of LSM5 in progression of colon cancer and the potential underlying mechanism involved.AIM To determine the role of LSM5 in the progression of colon cancer and the potential underlying mechanism involved.METHODS The Gene Expression Profiling Interactive Analysis database and the Human Protein Atlas website were used for LSM5 expression analysis and prognosis analysis.Real-time quantitative polymerase chain reaction and Western blotting were utilized to detect the expression of mRNAs and proteins.A lentivirus targeting LSM5 was constructed and transfected into colon cancer cells to silence LSM5 expression.Proliferation and apoptosis assays were also conducted to evaluate the growth of the colon cancer cells.Human GeneChip assay and bioinformatics analysis were performed to identify the potential underlying mechanism of LSM5 in colon cancer.RESULTS LSM5 was highly expressed in tumor tissue and colon cancer cells.A high expression level of LSM5 was related to poor prognosis in patients with colon cancer.Knockdown of LSM5 suppressed proliferation and promoted apoptosis in colon cancer cells.Silencing of LSM5 also facilitates the expression of p53,cyclin-dependent kinase inhibitor 1A(CDKN1A)and tumor necrosis factor receptor superfamily 10B(TNFRSF10B).The inhibitory effect of LSM5 knockdown on the growth of colon cancer cells was associated with the upregulation of p53,CDKN1A and TNFRSF10B.CONCLUSION LSM5 knockdown inhibited the proliferation and facilitated the apoptosis of colon cancer cells by upregulating p53,CDKN1A and TNFRSF10B.
基金the Scientific Research Project of Anhui Provincial Health Commission in 2021(#AHWJ2021b109 to LS)Scientific and Technological Research Program of Chongqing Municipal Education Commission(#KJZD-K201900402 to TZ)+1 种基金Special Fund for Wannan Medical College Scholar Project(#WK2021F07)Educational Commission of Anhui Province of China(2022AH051241).
文摘The role of lncRNA KCNQ1 opposite strand/antisense transcript 1(KCNQ1OT1)in colon cancer involves various tumorigenic processes and has been studed widely.However,the mechanism by which it promotes colon cancer remains unclear.Retrovirnl vector pSEB61 was retroftted in established HCT116 siKCN and SW480-siKCN cells to silence KCNQ1 OT1.Cellular proliferation was measured using CCK8 assay,and flow cytometry(FCM)detected cell cydle changes.RNA sequencing(RNA Seq)analysis showed differentially expressed genes(DEGs).Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses were carried out to analyze enriched functions and signaling pathways.RT-qPCR,immunofluorescence,and western blotting were carried out to validate downstream gene expressions.The effects of tumorigenesis were evaluated in BALB/c nude mice by tumor xenografts.Our data revealed that the silencing of KONQ1OT1 in HCT116 and SW480 cells slowed cell growth and decreased the number of cells in the G2/M phase.RNA-Seq analysis showed the data of DEGs enriched in various GO and KEGG pathways such as DNA replication and cell cyde.RT qPCR,immunofluorescence,and western blotting confirmed downstream CCNE2 and PCNA gene expressions.HCT116 siKCN cells signifcantly suppressed tumorigenesis in BALB/c nude mice.Our study suggests that lncRNA KCNQ1OT1 may provide a promising therapeutic strategy for colon cancer.
基金Supported by the General Project of Medical and Health Technology Plan of Zhejiang Province,No.2020KY845.
文摘BACKGROUND Limited knowledge exists regarding the casual associations linking blood metabolites and the risk of developing colorectal cancer.AIM To investigate causal associations between blood metabolites and colon cancer.METHODS The study utilized a two-sample Mendelian randomization(MR)analysis to investigate the causal impact of 486 blood metabolites on colorectal cancer.The primary method of analysis used was the inverse variance weighted model.To further validate the results several sensitivity analyses were performed,including Cochran's Q test,MR-Egger intercept test,and MR robust adjusted profile score.These additional analyses were conducted to ensure the reliability and robustness of the findings.RESULTS After rigorous selection for genetic variation,486 blood metabolites were included in the MR analysis.We found Mannose[odds ratio(OR)=2.09(1.10-3.97),P=0.024],N-acetylglycine[OR=3.14(1.78-5.53),P=7.54×10^(-8)],X-11593-O-methylascorbate[OR=1.68(1.04-2.72),P=0.034],1-arachidonoylglycerophosphocholine[OR=4.23(2.51-7.12),P=6.35×10^(-8)]and 1-arachidonoylglycerophosphoethanolamine 4[OR=3.99(1.17-13.54),P=0.027]were positively causally associated with colorectal cancer,and we also found a negative causal relationship between Tyrosine[OR=0.08(0.01-0.63),P=0.014],Urate[OR=0.25(0.10-0.62),P=0.003],N-acetylglycine[0.73(0.54-0.98),P=0.033],X-12092[OR=0.89(0.81-0.99),P=0.028],Succinylcarnitine[OR=0.48(0.27-0.84),P=0.09]with colorectal cancer.A series of sensitivity analyses were performed to confirm the rigidity of the results.CONCLUSION This study showed a causal relationship between 10 blood metabolites and colorectal cancer,of which 5 blood metabolites were found to be causal for the development of colorectal cancer and were confirmed as risk factors.The other five blood metabolites are protective factors.
基金Supported by National Natural Science Foundation of China,No.82360329Inner Mongolia Medical University General Project,No.YKD2023MS047Inner Mongolia Health Commission Science and Technology Plan Project,No.202201275.
文摘BACKGROUND Colorectal cancer has a low 5-year survival rate and high mortality.Humanβ-defensin-1(hBD-1)may play an integral function in the innate immune system,contributing to the recognition and destruction of cancer cells.Long non-coding RNAs(lncRNAs)are involved in the process of cell differentiation and growth.AIM To investigate the effect of hBD-1 on the mammalian target of rapamycin(mTOR)pathway and autophagy in human colon cancer SW620 cells.METHODS CCK8 assay was utilized for the detection of cell proliferation and determination of the optimal drug concentration.Colony formation assay was employed to assess the effect of hBD-1 on SW620 cell proliferation.Bioinformatics was used to screen potentially biologically significant lncRNAs related to the mTOR pathway.Additionally,p-mTOR(Ser2448),Beclin1,and LC3II/I expression levels in SW620 cells were assessed through Western blot analysis.RESULTS hBD-1 inhibited the proliferative ability of SW620 cells,as evidenced by the reduction in the colony formation capacity of SW620 cells upon exposure to hBD-1.hBD-1 decreased the expression of p-mTOR(Ser2448)protein and increased the expression of Beclin1 and LC3II/I protein.Furthermore,bioinformatics analysis identified seven lncRNAs(2 upregulated and 5 downregulated)related to the mTOR pathway.The lncRNA TCONS_00014506 was ultimately selected.Following the inhibition of the lncRNA TCONS_00014506,exposure to hBD-1 inhibited p-mTOR(Ser2448)and promoted Beclin1 and LC3II/I protein expression.CONCLUSION hBD-1 inhibits the mTOR pathway and promotes autophagy by upregulating the expression of the lncRNA TCONS_00014506 in SW620 cells.
文摘BACKGROUND Colon cancer(CC)occurrence and progression are considerably influenced by the tumor microenvironment.However,the exact underlying regulatory mechanisms remain unclear.AIM To investigate immune infiltration-related differentially expressed genes(DEGs)in CC and specifically explored the role and potential molecular mechanisms of complement factor I(CFI).METHODS Immune infiltration-associated DEGs were screened for CC using bioinformatics.Quantitative reverse transcription polymerase chain reaction was used to examine hub DEGs expression in the CC cell lines.Stable CFI-knockdown HT29 and HCT116 cell lines were constructed,and the diverse roles of CFI in vitro were assessed using CCK-8,5-ethynyl-2’-deoxyuridine,wound healing,and transwell assays.Hematoxylin and eosin staining and immunohistochemistry staining were employed to evaluate the influence of CFI on the tumorigenesis of CC xenograft models constructed using BALB/c male nude mice.Key proteins associated with glycolysis and the Wnt pathway were measured using western blotting.RESULTS Six key immune infiltration-related DEGs were screened,among which the expression of CFI,complement factor B,lymphoid enhancer binding factor 1,and SRY-related high-mobility-group box 4 was upregulated,whereas that of fatty acid-binding protein 1,and bone morphogenic protein-2 was downregulated.Furthermore,CFI could be used as a diagnostic biomarker for CC.Functionally,CFI silencing inhibited CC cell proliferation,migration,invasion,and tumor growth.Mechanistically,CFI knockdown downregulated the expression of key glycolysis-related proteins(glucose transporter type 1,hexokinase 2,lactate dehydrogenase A,and pyruvate kinase M2)and the Wnt pathway-related proteins(β-catenin and c-Myc).Further investigation indicated that CFI knockdown inhibited glycolysis in CC by blocking the Wnt/β-catenin/c-Myc pathway.CONCLUSION The findings of the present study demonstrate that CFI plays a crucial role in CC development by influencing glycolysis and the Wnt/β-catenin/c-Myc pathway,indicating that it could serve as a promising target for therapeutic intervention in CC.
文摘In this editorial we comment on the manuscript,describing management and surveillance strategies in synchronous and metachronous,gastric and colon cancers.Synchronous or metachronous primary malignancies at different sites of the gastrointestinal tract pose a unique diagnostic and therapeutic challenge.Multidisciplinary services and strategies are required for the management of multiple site primary malignancies,to provide the best oncological outcomes.Although this study highlights the dual cancers in 76 sporadic cases,the authors excluded 55 patients due to combination of factors which includes;incomplete clinical data,genetic syndrome,gastric stump cancers.In addition,the authors did not elaborate if any patients presented with signet ring cell morphology,E-cadherin mutations or presence of inflammatory bowel disease.Genetic and mutational errors and epithelial field defects from chronic inflammatory diseases of the gastrointestinal tract are important when considering synchronous gastric and colonic cancers.We will briefly discuss these in this editorial.
基金Supported by the National Natural Science Foundation of China,No.82160405Jiangxi Provincial Natural Science Foundation,No.20232BAB206131,No.20212ACB206016,and No.20224BAB206114+1 种基金Jiangxi Provincial Health Commission Project,No.202310887the Development Fund of Jiangxi Cancer Hospital,No.2021J10.
文摘BACKGROUND Heterogeneous ribonucleoprotein A1(hnRNPA1)has been reported to enhance the Warburg effect and promote colon cancer(CC)cell proliferation,but the role and mechanism of the miR-490-3p/hnRNPA1-b/PKM2 axis in CC have not yet been elucidated.AIM To investigate the role and mechanism of a novel miR-490-3p/hnRNPA1-b/PKM2 axis in enhancing the Warburg effect and promoting CC cell proliferation through the PI3K/AKT pathway.METHODS Paraffin-embedded pathological sections from 220 CC patients were collected and subjected to immunohistochemical analysis to determine the expression of hnRNPA1-b.The relationship between the expression values and the clinicopathological features of the patients was investigated.Differences in mRNA expression were analyzed using quantitative real-time polymerase chain reaction,while differences in protein expression were analyzed using western blot.Cell proliferation was evaluated using the cell counting kit-8 and 5-ethynyl-2’-deoxyuridine assays,and cell cycle and apoptosis were detected using flow cytometric assays.The targeted binding of miR-490-3p to hnRNPA1-b was validated using a dual luciferase reporter assay.The Warburg effect was evaluated by glucose uptake and lactic acid production assays.RESULTS The expression of hnRNPA1-b was significantly increased in CC tissues and cells compared to normal controls(P<0.05).Immunohistochemical results demonstrated significant variations in the expression of the hnRNPA1-b antigen in different stages of CC,including stage I,II-III,and IV.Furthermore,the clinicopathologic characterization revealed a significant correlation between hnRNPA1-b expression and clinical stage as well as T classification.HnRNPA1-b was found to enhance the Warburg effect through the PI3K/AKT pathway,thereby promoting proliferation of HCT116 and SW620 cells.However,the proliferation of HCT116 and SW620 cells was inhibited when miR-490-3p targeted and bound to hnRNPA1-b,effectively blocking the Warburg effect.CONCLUSION These findings suggest that the novel miR-490-3p/hnRNPA1-b/PKM2 axis could provide a new strategy for the diagnosis and treatment of CC.
文摘In this editorial,I commented on the paper by Lin et al,published in this issue of the World Journal of Gastrointestinal Oncology.The work aimed at analysing the clinicopathologic characteristics and prognosis of synchronous and metachronous cancers in patients with dual primary gastric and colorectal cancer(CRC).The authors concluded the necessity for regular surveillance for metachronous cancer during postoperative follow-up and reported the prognosis is influenced by the gastric cancer(GC)stage rather than the CRC stage.Although surveillance was recommended in the conclusion,the authors did not explore this area in their study and did not include tests used for such surveillance.This editorial focuses on the most characterized gastrointestinal cancer susceptibility syndromes concerning dual gastric and CRCs.These include hereditary diffuse GC,familial adenomatous polyposis,hereditary nonpolyposis colon cancer,Lynch syndrome,and three major hamartomatous polyposis syndromes associated with CRC and GC,namely Peutz-Jeghers syndrome,juvenile polyposis syndrome,and PTEN hamartoma syndrome.Careful assessment of these syndromes/conditions,including inheritance,risk of gastric and colorectal or other cancer development,genetic mutations and recommended genetic investigations,is crucial for optimum management of these patients.
基金Supported by National Nature Science Foundation of China,No.82100195China Postdoctoral Science Foundation,No.2021M700777Medical Research Project of Foshan Municipal Health Bureau,No.20230349.
文摘BACKGROUND Colon cancer is acknowledged as one of the most common malignancies worldwide,ranking third in United States regarding incidence and mortality.Notably,approximately 40%of colon cancer cases harbor oncogenic KRAS mutations,resulting in the continuous activation of epidermal growth factor receptor signaling.AIM To investigate the key pathogenic genes in KRAS mutant colon cancer holds considerable importance.METHODS Weighted gene co-expression network analysis,in combination with additional bioinformatics analysis,were conducted to screen the key factors driving the progression of KRAS mutant colon cancer.Meanwhile,various in vitro experiments were also conducted to explore the biological function of transglutaminase 2(TGM2).RESULTS Integrated analysis demonstrated that TGM2 acted as an independent prognostic factor for progression-free survival.Immunohistochemical analysis on tissue microarrays revealed that TGM2 was associated with an elevated probability of perineural invasion in patients with KRAS mutant colon cancer.Additionally,biological roles of the key gene TGM2 was also assessed,suggesting that the downregulation of TGM2 attenuated the proliferation,invasion,and migration of the KRAS mutant colon cancer cell line.CONCLUSION This study underscores the potential significance of TGM2 in the progression of KRAS mutant colon cancer.This insight not only offers a theoretical foundation for therapeutic approaches but also highlights the need for additional clinical trials and fundamental research to support our preliminary findings.
文摘BACKGROUND Colon cancer(CC)has a high incidence rate.Radical resection is the main treatment method for CC;however,liver metastasis(LM)often occurs post-surgery.The liver contains both innate and adaptive immune cells that monitor and remove abnormal cells and pathogens.Before LM,tumor cells secrete cytokines and exosomes to adjust the immune microenvironment of the liver,thus forming an inhibitory immune microenvironment for colonization by circulating tumor cells.This indicates that the immune state of patients with CC plays a crucial role in the occurrence and progression of LM.AIM To observe and analyze the relationship between immune status and expression of tumor factors in patients with LM of CC,and to provide a scientific interven-tion method for promoting the patient prognosis.METHODS A retrospective analysis was performed.The baseline data of 100 patients with CC and 100 patients with CC who suffered from postoperative LM and were admitted to our hospital from May 2021 to May 2023 were included in the non-occurrence and occurrence groups,respectively.The immune status of the pa-tients and the expression of tumor factor-related indicators in the two groups were compared,and the predictive value of the indicators for postoperative LM in patients with CC was analyzed.RESULTS Compared with the non-occurrence group,the expression of serum carcinoem-bryonic antigen(CEA),CA19-9,CA242,CA72-4 and CA50 in patients in the occurrence group were significantly higher,while the expression of CD3+,CD4+,CD8+,natural killer(NK)and CD4+/CD25 in patients in the occurrence group were significantly lower(P<0.05).No significant difference was observed in other baseline data between groups(P>0.05).Multivariate logistic regression model analysis revealed that the expressions of CEA,CA19-9,CA242,CA72-4,CA50,CD3+,CD4+,CD8+,NK,and CD4+/CD25 were associated with the LM in patients with CC.High expressions of serum CEA,CA19-9,CA242,CA72-4 and CA50,and low expressions of CD3+,CD4+,CD8+,NK,and CD4+/CD25 in patients with CC were risk factors for LM(OR>1,P<0.05).The receiver operating characteristic curve showed that the area under curve for CEA,CA19-9,CA242,CA72-4,CA50,CD3+,CD4+,CD8+,NK,and CD4+/CD25 in the prediction of LM in patients with CC were all>0.80,with a high predictive value.CONCLUSION The expression of tumor factors and immune state-related indices in patients with CC is closely associated with the occurrence of LM.
基金This study was reviewed and approved by the Ethics Review Committee of the Research Ethics Committee,Tokai University School of Medicine(23RC011).
文摘BACKGROUND Although intracorporeal anastomosis(IA)for colon cancer requires longer operative time than extracorporeal anastomosis(EA),its short-term postoperative results,such as early recovery of bowel movement,have been reported to be equal or better.As IA requires opening the intestinal tract in the abdominal cavity under pneumoperitoneum,there are concerns about intraperitoneal bacterial infection and recurrence of peritoneal dissemination due to the spread of bacteria and tumor cells.However,intraperitoneal bacterial contamination and medium-term oncological outcomes have not been clarified.abdominal cavity in IA.METHODS Of 127 patients who underwent laparoscopic colon resection for colon cancer from April 2015 to December 2020,75 underwent EA(EA group),and 52 underwent IA(IA group).After propensity score matching,the primary endpoint was 3-year disease-free survival rates,and secondary endpoints were 3-year overall survival rates,type of recurrence,surgical site infection(SSI)incidence,number of days on antibiotics,and postoperative biological responses.RESULTS Three-year disease-free survival rates did not significantly differ between the IA and EA groups(87.2%and 82.7%,respectively,P=0.4473).The 3-year overall survival rates also did not significantly differ between the IA and EA groups(94.7%and 94.7%,respectively;P=0.9891).There was no difference in the type of recurrence between the two groups.In addition,there were no significant differences in SSI incidence or the number of days on antibiotics;however,postoperative biological responses,such as the white blood cell count(10200 vs 8650/mm^(3),P=0.0068),C-reactive protein(6.8 vs 4.5 mg/dL,P=0.0011),and body temperature(37.7 vs 37.5℃,P=0.0079),were significantly higher in the IA group.CONCLUSION IA is an anastomotic technique that should be widely performed because its risk of intraperitoneal bacterial contamination and medium-term oncological outcomes are comparable to those of EA.
基金reviewed and approved by the Institutional Review Board of Zhejiang Provincial People’s Hospital(Approval No.2023-338).
文摘BACKGROUND Colon cancer is one of the most common malignant tumors of the digestive system.Liver metastasis after colon cancer surgery is the primary cause of death in patients with colon cancer.AIM To construct a novel nomogram model including various factors to predict liver metastasis after colon cancer surgery.METHODS We retrospectively analyzed 242 patients with colon cancer who were admitted and underwent radical resection for colon cancer in Zhejiang Provincial People’s Hospital from December 2019 to December 2022.Patients were divided into liver metastasis and non-liver metastasis groups.Sex,age,and other general and clinicopathological data(preoperative blood routine and biochemical test indexes)were compared.The risk factors for liver metastasis were analyzed using singlefactor and multifactorial logistic regression.A predictive model was then constructed and evaluated for efficacy.RESULTS Systemic inflammatory index(SII),C-reactive protein/albumin ratio(CAR),red blood cell distribution width(RDW),alanine aminotransferase,preoperative carcinoembryonic antigen level,and lymphatic metastasis were different between groups(P<0.05).SII,CAR,and RDW were risk factors for liver metastasis after colon cancer surgery(P<0.05).The area under the curve was 0.93 for the column-line diagram prediction model constructed based on these risk factors to distinguish whether liver metastasis occurred postoperatively.The actual curve of the column-line diagram predicting the risk of postoperative liver metastasis was close to the ideal curve,with good agreement.The prediction model curves in the decision curve analysis showed higher net benefits for a larger threshold range than those in extreme cases,indicating that the model is safer.CONCLUSION Liver metastases after colorectal cancer surgery could be well predicted by a nomogram based on the SII,CAR,and RDW.