Study on Proteomics in Hepatic Metastasis of Colorectal neoplasms

Colorectal cancer is one of the most frequent cancers in the world. Hepatic metastasis is the most common site metastatic disease and dominant cause of death in colorectal cancer patients. In the large majority of cases, cell dysfunction in CRC results from multiple rather than single, gene interactions, so to be able to predict occurrence of disease and treatment outcome, more studies on comparative proteomics are needed both in sporadic and in hereditary colorectal cancer. This article is about the proteomic study on hepatic metastasis of colorectal cancer which helps to identify the specific proteins that play important roles in hepatic metastasis. The study of protein molecules with their expressions correlated to the metastatic process would help to understand the metastatic mechanisms and thus facilitate the development of strategies for the therapeutic interventions and clinical markagement of cancer.

Impact of preoperative inflammatory and nutritional markers on the prognosis of patients with peritoneal metastasis of colorectal cancer

BACKGROUND Identifying patients with peritoneal metastasis(PMs)of colorectal cancer(CRC)who will benefit from cytoreductive surgery and hyperthermic intraperitoneal chemotherapy is crucial before surgery.Inflammatory and nutritional indicators play essential roles in cancer development and metastasis.AIM To investigate the association of preoperative inflammatory and nutritional markers with prognosis in patients with CRC-PM.METHODS We included 133 patients diagnosed with CRC-PM between July 2012 and July 2018.Patients’demographics,overall survival(OS),and preoperative inflammatory and nutritional markers were evaluated.The Kaplan-Meier method and log-rank test were used to estimate differences.RESULTS Of the 133 patients,94(70.6%)had normal hemoglobin(Hb)and 54(40.6%)had a high neutrophil-to-lymphocyte ratio(NLR).The median OS(mOS)was significantly lower for patients with high NLR(7.9 months)than for those with low NLR(25.4 months;P=0.002).Similarly,patients with normal Hb had a longer mOS(18.5 months)than those with low Hb(6.3 months;P<0.001).Multivariate analysis identified age,carbohydrate antigen 199 levels,NLR,Hb,and peritoneal cancer index as independent predictors of OS.Based on these findings,a nomogram was constructed,which demonstrated a good capacity for prediction,with a C-index of 0.715(95%confidence interval:0.684-0.740).Furthermore,the 1-and 2-year survival calibration plots showed good agreement between predicted and actual OS rates.The areas under the curve for the 1-and 2-year survival predictions of the nomogram were 0.6238 and 0.6234,respectively.CONCLUSION High NLR and low Hb were identified as independent predictive risk factors for poor prognosis in patients with CRC-PM.The established nomogram demonstrated high accuracy in predicting OS for patients with CRC-PM,indicating its potential as a valuable prognostic tool for this patient population.

Microbiota in colorectal cancer related to liver metastasis

The prevalence of colorectal cancer(CRC) is increasing annually and metastasis is the principal cause of death in patients with CRC, with the liver being the most frequently affected site. Many studies have shown a strong interplay between the gut flora, particularly Fusobacterium nucleatum(F. nucleatum), Escherichia coli, and Bacteroides fragilis, and the development of gut tumors. Some strains can induce gut inflammation and produce toxins that directly harm gut epithelial cells, ultimately accelerating the onset and progression of CRC. However,little clinical evidence exists on the specific interplay between the gut microflora and colorectal cancer liver metastasis(CRLM). Some research showed the existence of viable F. nucleatum in distant metastasis of CRC.Subsequently, gut microbiota products, such as lipopolysaccharides, sodium butyrate, and protein cathepsin K, were also found to affect the development of CRC. This article summarizes the mechanism and research status of the interplay between gut microflora and CRLM, discusses the importance of gut microflora in the treatment of CRLM, and proposes a new approach to understanding the mechanism of CRLM and potential treatments for the microbiome. It is anticipated that the gut microbiota will be a formidable therapeutic and prophylactic tool for treating and preventing CRLM.

Current landscape of preoperative neoadjuvant therapies for initial resectable colorectal cancer liver metastasis

Colorectal cancer liver metastasis(CRLM)presents a clinical challenge,and optimizing treatment strategies is crucial for improving patient outcomes.Surgical resection,a key element in achieving prolonged survival,is often linked to a heightened risk of recurrence.Acknowledging the potential benefits of preoperative neoadjuvant chemotherapy in managing resectable liver metastases,this approach has gained attention for its role in tumor downsizing,assessing biological behavior,and reducing the risk of postoperative recurrence.However,the use of neoadjuvant chemotherapy in initially resectable CRLM sparks ongoing debates.The balance between tumor reduction and the risk of hepatic injury,coupled with concerns about delaying surgery,necessitates a nuanced approach.This article explores recent research insights and draws upon the practical experiences at our center to address critical issues regarding considerations for initially resectable cases.Examining the criteria for patient selection and the judicious choice of neoadjuvant regimens are pivotal areas of discussion.Striking the right balance between maximizing treatment efficacy and minimizing adverse effects is imperative.The dynamic landscape of precision medicine is also reflected in the evolving role of gene testing,such as RAS/BRAF and PIK3CA,in tailoring neoadjuvant regimens.Furthermore,the review emphasizes the need for a multidisciplinary approach to navigate the comp-lexities of CRLM.Integrating technical expertise and biological insights is crucial in refining neoadjuvant strategies.The management of progression following neoadjuvant chemotherapy requires a tailored approach,acknowledging the diverse biological behaviors that may emerge.In conclusion,this review aims to provide a comprehensive perspective on the considerations,challenges,and advancements in the use of neoadjuvant chemotherapy for initially resectable CRLM.By combining evidencebased insights with practical experiences,we aspire to contribute to the ongoing discourse on refining treatment paradigms for improved outcomes in patients with CRLM.

Research progress on the effect of pyroptosis on the occurrence,development,invasion and metastasis of colorectal cancer

Pyroptosis is a type of programmed cell death mediated by gasdermines(GSDMs).The N-terminal domain of GSDMs forms pores in the plasma membrane,causing cell membrane rupture and the release of cell contents,leading to an inflammatory response and mediating pyrodeath.Pyroptosis plays an important role in inflammatory diseases and malignant tumors.With the further study of pyroptosis,an increasing number of studies have shown that the pyroptosis pathway can regulate the tumor microenvironment and antitumor immunity of colorectal cancer and is closely related to the occurrence,development,treatment and prognosis of colorectal cancer.This review aimed to explore the molecular mechanism of pyroptosis and the role of pyroptosis in the occurrence,development,treatment and prognosis of colorectal cancer(CRC)and to provide ideas for the clinical diagnosis and treatment of CRC.

Correlation between TEX14 and ADAM17 expressions in colorectal cancer tissues of elderly patients and neoplasm staging,invasion,and metastasis

BACKGROUND Colorectal cancer(CRC)is one of the most frequently encountered malignant tumors in clinical settings.Proteins encoded by the testis-expressed gene 14(TEX14)are imperative for spermatogenesis,necessitating intercellular bridges between germ cells.Anomalous expression of TEX14 has also been associated with the proliferation and differentiation of certain tumor cells.Recombinant A disintegrin and metalloprotease 17(ADAM17)is known as a membrane-bound protease that regulates cellular activities and signal transduction by hydrolyzing various substrate proteins on the cell membrane.We hypothesize that TEX14 and ADAM17 may serve as potential biomarkers influencing the staging,invasion,and metastasis of CRC.AIM To probe the correlation between TEX17 and ADAM17 profiles in the CRC tissues of elderly patients and their association with CRC staging,invasion,and metastasis.METHODS We gathered data from 86 elderly patients diagnosed pathologically with CRC between April 2020 and December 2023.For each patient,one sample of cancer tissue and one sample of adjacent normal tissue were harvested.Real-time fluorescence quantitative PCR measured the mRNA profiles of TEX14 and ADAM17.Immunohistochemistry ascertained the positivity rates of TEX14 and ADAM17 expressions.Clinical pathological features of neoplasm staging,invasion,and metastasis were collected,and the association between TEX14 and ADAM17 expressions and clinical pathology was evaluated.RESULTS The mRNA and expression profiles of TEX14 and ADAM17 were significantly elevated in CRC tissues.The positivity rates of TEX14 and ADAM17 proteins in CRC tissues were 70.93%and 77.91%,respectively.There were no significant differences in age,sex,pathological type,and tumor diameter between TEX14 and ADAM17-positive and-negative patients.Patients with higher tumor differentiation degree,deeper infiltration and TNM stages ranging from III to IV exhibited higher positivity rates of TEX14 and ADAM17.Patients with lymph node metastasis and distant metastasis showed higher positivity rates of TEX14 and ADAM17 than those without.Positive expressions of TEX14 and ADAM17 were highly correlated with tumor staging,invasion,and metastasis.CONCLUSION TEX14 and ADAM17 profiles were significantly elevated in the CRC tissues of elderly patients,and their high expressions were associated with tumor staging,invasion,and metastasis.

Value of glucose transport protein 1 expression in detecting lymph node metastasis in patients with colorectal cancer

BACKGROUND There are limited data on the use of glucose transport protein 1(GLUT-1)expre-ssion as a biomarker for predicting lymph node metastasis in patients with colorectal cancer.GLUT-1 and GLUT-3,hexokinase(HK)-II,and hypoxia-induced factor(HIF)-1 expressions may be useful biomarkers for detecting primary tumors and lymph node metastasis when combined with fluorodeoxyglucose(FDG)uptake on positron emission tomography/computed tomography(PET/CT).AIM To evaluate GLUT-1,GLUT-3,HK-II,and HIF-1 expressions as biomarkers for detecting primary tumors and lymph node metastasis with 18F-FDG-PET/CT.METHODS This retrospective study included 169 patients with colorectal cancer who underwent colectomy and preoperative 18F-FDG-PET/CT at Chungbuk National University Hospital between January 2009 and May 2012.Two tissue cores from the central and peripheral areas of the tumors were obtained and were examined by a dedicated pathologist,and the expressions of GLUT-1,GLUT-3,HK-II,and HIF-1 were determined using immunohisto-chemical staining.We analyzed the correlations among their expressions,various clinicopathological factors,and the maximum standardized uptake value(SUVmax)of PET/CT.RESULTS GLUT-1 was found at the center or periphery of the tumors in 109(64.5%)of the 169 patients.GLUT-1 positivity was significantly correlated with the SUVmax of the primary tumor and lymph nodes,regardless of the biopsy site(tumor center,P<0.001 and P=0.012;tumor periphery,P=0.030 and P=0.010,respectively).GLUT-1 positivity and negativity were associated with higher and lower sensitivities of PET/CT,respectively,for the detection of lymph node metastasis,regardless of the biopsy site.GLUT3,HK-II,and HIF-1 expressions were not significantly correlated with the SUVmax of the primary tumor and lymph nodes.CONCLUSION GLUT-1 expression was significantly correlated with the SUVmax of 18F-FDG-PET/CT for primary tumors and lymph nodes.Clinicians should consider GLUT-1 expression in preoperative endoscopic biopsy in interpreting PET/CT findings.

Erythropoietin-induced hepatocyte receptor A2 regulates effect of pyroptosis on gastrointestinal colorectal cancer occurrence and metastasis resistance

Erythropoietin-induced hepatocyte receptor A2(EphA2)is a receptor tyrosine kinase that plays a key role in the development and progression of a variety of tumors.This article reviews the expression of EphA2 in gastrointestinal(GI)colorectal cancer(CRC)and its regulation of pyroptosis.Pyroptosis is a form of programmed cell death that plays an important role in tumor suppression.Studies have shown that EphA2 regulates pyrodeath through various signaling pathways,affecting the occurrence,development and metastasis of GI CRC.The overexpression of EphA2 is closely related to the aggressiveness and metastasis of GI CRC,and the inhibition of EphA2 can induce pyrodeath and improve the sensitivity of cancer cells to treatment.In addition,EphA2 regulates intercellular communication and the microenvironment through interactions with other cytokines and receptors,further influencing cancer progression.The role of EphA2 in GI CRC and its underlying mechanisms provide us with new perspectives and potential therapeutic targets,which have important implications for future cancer treatment.

Histological Risk Factors for Lymph Node Metastasis in pT1 Colorectal Cancer:Does Submucosal Invasion Depth Really Matter?

Objective After endoscopic resection of colorectal cancer with submucosal invasion(pT1 CRC),additional surgical treatment is recommended if deep submucosal invasion(DSI)is present.This study aimed to further elucidate the risk factors for lymph node metastasis(LNM)in patients with pT1 CRC,especially the effect of DSI on LNM.Methods Patients with pT1 CRC who underwent lymph node dissection were selected.The Chi-square test and multivariate logistic regression were used to analyze the relationship between clinicopathological characteristics and LNM.The submucosal invasion depth(SID)was measured via 4 methods and analyzed with 3 cut-off values.Results Twenty-eight of the 239 patients presented with LNM(11.7%),and the independent risk factors for LNM included high histological grade(P=0.003),lymphovascular invasion(LVI)(P=0.004),intermediate to high budding(Bd 2/3)(P=0.008),and cancer gland rupture(CGR)(P=0.008).Moreover,the SID,width of submucosal invasion(WSI),and area of submucosal invasion(ASI)were not significantly different.When one,two,three or more risk factors were identified,the LNM rates were 1.1%(1/95),12.5%(7/56),and 48.8%(20/41),respectively.Conclusion Indicators such as the SID,WSI,and ASI are not risk factors for LNM and are subjective in their measurement,which renders them relatively inconvenient to apply in clinical practice.In contrast,histological grade,LVI,tumor budding and CGR are relatively straightforward to identify and have been demonstrated to be statistically significant.It would be prudent to focus on these histological factors rather than subjective measurements.

Prediction and analysis of albumin-bilirubin score combined with liver function index and carcinoembryonic antigen on liver metastasis of colorectal cancer

BACKGROUND Colorectal cancer(CRC)is a common malignant tumor,and liver metastasis is one of the main recurrence and metastasis modes that seriously affect patients’survival rate and quality of life.Indicators such as albumin bilirubin(ALBI)score,liver function index,and carcinoembryonic antigen(CEA)have shown some potential in the prediction of liver metastasis but have not been fully explored.AIM To evaluate its predictive value for liver metastasis of CRC by conducting the combined analysis of ALBI,liver function index,and CEA,and to provide a more accurate liver metastasis risk assessment tool for clinical treatment guidance.METHODS This study retrospectively analyzed the clinical data of patients with CRC who received surgical treatment in our hospital from January 2018 to July 2023 and were followed up for 24 months.According to the follow-up results,the enrolled patients were divided into a liver metastasis group and a nonliver metastasis group and randomly divided into a modeling group and a verification group at a ratio of 2:1.The risk factors for liver metastasis in patients with CRC were analyzed,a prediction model was constructed by least absolute shrinkage and selection operator(LASSO)logistic regression,internal validation was performed by the bootstrap method,the reliability of the prediction model was evaluated by subject-work characteristic curves,calibration curves,and clinical decision curves,and a column graph was drawn to show the prediction results.RESULTS Of 130 patients were enrolled in the modeling group and 65 patients were enrolled in the verification group out of the 195 patients with CRC who fulfilled the inclusion and exclusion criteria.Through LASSO regression variable screening and logistic regression analysis.The ALBI score,alanine aminotransferase(ALT),and CEA were found to be independent predictors of liver metastases in CRC patients[odds ratio(OR)=8.062,95%confidence interval(CI):2.545-25.540],(OR=1.037,95%CI:1.004-1.071)and(OR=1.025,95%CI:1.008-1.043).The area under the receiver operating characteristic curve(AUC)for the combined prediction of CRLM in the modeling group was 0.921,with a sensitivity of 78.0%and a specificity of 95.0%.The H-index was 0.921,and the H-L fit curve hadχ^(2)=0.851,a P value of 0.654,and a slope of the calibration curve approaching 1.This indicates that the model is extremely accurate,and the clinical decision curve demonstrates that it can be applied effectively in the real world.We conducted internal verification of one thousand resamplings of the modeling group data using the bootstrap method.The AUC was 0.913,while the accuracy was 0.869 and the kappa consistency was 0.709.The combination prediction of liver metastasis in patients with CRC in the verification group had an AUC of 0.918,sensitivity of 85.0%,specificity of 95.6%,C-index of 0.918,and an H-L fitting curve withχ^(2)=0.586,P=0.746.CONCLUSION The ALBI score,ALT level,and CEA level have a certain value in predicting liver metastasis in patients with CRC.These three criteria exhibit a high level of efficacy in forecasting liver metastases in patients diagnosed with CRC.The risk prediction model developed in this work shows great potential for practical application.

GLI1 and PTTG1 expression in colorectal carcinoma patients undergoing radical surgery and their correlation with lymph node metastasis

BACKGROUND Few studies have investigated the expression of GLI1 and PTTG1 in patients undergoing radical surgery for colorectal carcinoma(CRC)and their association with lymph node metastasis(LNM).Therefore,more relevant studies and analyses need to be conducted.AIM To explore GLI1 and PTTG1 expression in patients undergoing radical surgery for CRC and their correlation with LNM.METHODS This study selected 103 patients with CRC admitted to our hospital between April 2020 and April 2023.Sample specimens of CRC and adjacent tissues were collected to determine the positive rates and expression levels of GLI1 and PTTG1.The correlation of the two genes with patients’clinicopathological data(e.g.,LNM)was explored,and differences in GLI1 and PTTG1 expression between patients with LNM and those without were analyzed.Receiver operating characteristic(ROC)curves were plotted to evaluate the predictive potential of the two genes for LNM in patients with CRC.RESULTS Significantly higher positive rates and expression levels of GLI1 and PTTG1 wereobserved in CRC tissue samples compared with adjacent tissues.GLI1 and PTTG1 were strongly linked to LNM in patients undergoing radical surgery for CRC,with higher GLI1 and PTTG1 levels found in patients with LNM than in those without.The areas under the ROC curve of GLI1 and PTTG1 in assessing LNM in patients with CRC were 0.824 and 0.811,respectively.CONCLUSION GLI1 and PTTG1 expression was upregulated in patients undergoing radical surgery for CRC and are significantly related to LNM in these patients.Moreover,high GLI1 and PTTG1 expression can indicate LNM in patients with CRC undergoing radical surgery.The expression of both genes has certain diagnostic and therapeutic significance.

Adjuvant chemotherapy for isolated resectable colorectal lung metastasis: A retrospective study using inverse probability treatment weighting propensity analysis

BACKGROUND The benefit of adjuvant chemotherapy(ACT)for patients with no evidence of disease after pulmonary metastasis resection(PM)from colorectal cancer(CRC)remains controversial.AIM To assess the efficacy of ACT in patients after PM resection for CRC.METHODS This study included 96 patients who underwent pulmonary metastasectomy for CRC at a single institution between April 2008 and July 2023.The primary end-point was overall survival(OS);secondary endpoints included cancer-specific survival(CSS)and disease-free survival(DFS).An inverse probability of treat-ment-weighting(IPTW)analysis was conducted to address indication bias.Sur-vival outcomes compared using Kaplan-Meier curves,log-rank test,Cox regre-ssion and confirmed by propensity score-matching(PSM).RESULTS With a median follow-up of 27.5 months(range,18.3-50.4 months),the 5-year OS,CSS and DFS were 72.0%,74.4%and 51.3%,respectively.ACT had no significant effect on OS after PM resection from CRC[original cohort:P=0.08;IPTW:P=0.15].No differences were observed for CSS(P=0.12)and DFS(P=0.68)between the ACT and non-ACT groups.Multivariate analysis showed no association of ACT with better survival,while sublobar resection(HR=0.45;95%CI:0.20-1.00,P=0.049)and longer disease-free interval(HR=0.45;95%CI:0.20-0.98,P=0.044)were associated with improved survival.CONCLUSION ACT does not improve survival after PM resection for CRC.Further well-designed randomized controlled trials are needed to determine the optimal ACT regimen and duration.

Machine learning prediction model for gray-level co-occurrence matrix features of synchronous liver metastasis in colorectal cancer

BACKGROUND Synchronous liver metastasis(SLM)is a significant contributor to morbidity in colorectal cancer(CRC).There are no effective predictive device integration algorithms to predict adverse SLM events during the diagnosis of CRC.AIM To explore the risk factors for SLM in CRC and construct a visual prediction model based on gray-level co-occurrence matrix(GLCM)features collected from magnetic resonance imaging(MRI).METHODS Our study retrospectively enrolled 392 patients with CRC from Yichang Central People’s Hospital from January 2015 to May 2023.Patients were randomly divided into a training and validation group(3:7).The clinical parameters and GLCM features extracted from MRI were included as candidate variables.The prediction model was constructed using a generalized linear regression model,random forest model(RFM),and artificial neural network model.Receiver operating characteristic curves and decision curves were used to evaluate the prediction model.RESULTS Among the 392 patients,48 had SLM(12.24%).We obtained fourteen GLCM imaging data for variable screening of SLM prediction models.Inverse difference,mean sum,sum entropy,sum variance,sum of squares,energy,and difference variance were listed as candidate variables,and the prediction efficiency(area under the curve)of the subsequent RFM in the training set and internal validation set was 0.917[95%confidence interval(95%CI):0.866-0.968]and 0.09(95%CI:0.858-0.960),respectively.CONCLUSION A predictive model combining GLCM image features with machine learning can predict SLM in CRC.This model can assist clinicians in making timely and personalized clinical decisions.

Colonoscopy plays an important role in detecting colorectal neoplasms in patients with gastric neoplasms

BACKGROUND Gastric cancer(GC)and colorectal cancer(CRC)are the fifth and third most common cancer worldwide,respectively.Nowadays,GC is reported to have a potential predictive value for CRC,especially for advanced CRC.AIM To evaluate the necessity of colonoscopy for gastric neoplasm(GN)patients.METHODS Four databases,including PubMed,EMBASE,the Cochrane Library,and Ovid,were used to perform the search strategy on May 2,2023.The prevalence of colorectal neoplasms(CRN)and baseline characteristics were compared between the neoplasm group and the control group.Continuous variables are expressed as the mean difference and standard deviation.Relationships of categorical variables in the two groups are expressed as odds ratios(OR)and 95%confidence intervals(95%CIs).Subgroup analysis according to different kinds of GNs was conducted for more in-depth analysis.The results of this study are represented by forest plots.Publication bias was evaluated by a funnel plot.All data analyses were performed by STATA SE 16.0 software.RESULTS A total of 3018 patients with GNs and 3905 healthy controls(age and sex matched)were enrolled for analysis.After comparing the prevalence of CRNs between the two groups,CRNs were detected significantly more frequently in GN patients than in controls(OR=1.69,95%CI=1.28 to 2.23,I^(2)=85.12%,P=0.00),especially in patients with GC(OR=1.80,95%CI=1.49 to 2.18,I^(2)=25.55%,P<0.1).Moreover,other risk factors including age(OR=1.08,95%CI=1.00 to 1.17,I^(2)=90.13%,P=0.00)and male sex(OR=2.31,95%CI=1.26 to 4.22,I^(2)=87.35%,P=0.00),were related to the prevalence of CRNs.For patients in the GN group,body mass index(BMI,OR=0.88,95%CI=0.80 to 0.98,I^(2)=0.00%,P=0.92)and smoking(OR=1.03,95%CI=1.01 to 1.05,I^(2)=0.00%,P=0.57)were protective and risk factors for CRNs,respectively.CONCLUSION Patients are recommended to undergo colonoscopy when diagnosed with GNs,especially GC patients with a low BMI and a history of smoking.

Hepatectomy vs radiofrequency ablation for colorectal liver metastasis:A propensity score analysis

AIM:To compare outcomes from radiofrequency ablation(RFA) and hepatectomy for treatment of colorectal liver metastasis(CRLM).METHODS:From January 2000 to December 2009,408 patients underwent curative intent treatment for CRLM.We excluded patients using the criteria:size of CRLM > 3 cm,number of CRLM ≥ 5,percutaneous RFA,follow-up period < 12 mo,double primary cancer,or treatment with both RFA and hepatectomy.We matched 51 patients who underwent RFA with 102 patients who underwent hepatectomy by propensity scores.RESULTS:The median follow-up period was 45 mo(range,12 mo to 158 mo).Hepatic recurrence was more frequent in the RFA than the hepatectomy group(P = 0.021) although extrahepatic recurrence curves were similar(P = 0.716).Survival curves of hepatectomy group were better than that of RFA for multiple,large(> 2 cm) CRLM(P = 0.034).However,survival curves were similar for single or small(≤ 2 cm) CRLM(P = 0.714,P = 0.740).CONCLUSION:Hepatectomy is better than RFA for the treatment of CRLM.However,RFA might be suitable for selected patients with single,small(≤ 2 cm) CRLM.

Risk factors for bleeding after endoscopic submucosal dissection of colorectal neoplasms

AIM: To investigate the risk factors for delayed bleeding following endoscopic submucosal dissection (ESD) treatment for colorectal neoplasms.

Micro RNAs in colorectal cancer:Role in metastasis and clinical perspectives

Colorectal cancer (CRC) is the third most common malignancy and the third leading cause of cancer related deaths in the United States. Almost 90% of the patients diagnosed with CRC die due to metastases. MicroRNAs (miRNAs) are evolutionarily conserved molecules that modulate the expression of their target genes post-transcriptionally, and they may participate in various physiological and pathological processes including CRC metastasis by influencing various factors in the human body. Recently, the role miRNAs play throughout the CRC metastatic cascade has gain attention. Many studies have been published to link them with CRC metastasis. In this review, we will briefly discuss metastatic steps in the light of miRNAs, along with their target genes. We will discuss how the aberration in the expression of miRNAs leads to the formation of CRC by effecting the regulation of their target genes. As miRNAs are being exploited for diagnosis, prognosis, and monitoring of cancer and other diseases, their high tissue specificity and critical role in oncogenesis make them new biomarkers for the diagnosis and classification of cancer as well as for predicting patients&#x02019; outcome. MiRNA signatures have been identified for many human tumors including CRC, and miRNA-based therapies to treat cancer have been emphasized lately. These will also be discussed in this review.

Differential expression of serum miR-126,miR-141 and miR-21 as novel biomarkers for early detection of liver metastasis in colorectal cancer

Objective：MicroRNAs （miRNAs） have potential as diagnostic biomarkers in cancer.Evaluation of the association between miRNA expression patterns and early detection of liver metastasis in colorectal cancer （CRC） has not been reported.Methods：We investigated the expression of metastasis-associated miRs-31,335,206,141,126,200b,200c,21,Let7a,Let7b and Let7c in localized,liver-metastatic and other organ-metastatic CRC （OM-CRC）.Expressions of target miRNAs in serum were evaluated in 116 consecutive localized CRC （L-CRC）,72 synchronous liver-metastatic CRC （SLM-CRC） and 36 other OM-CRC by quantitative real-time PCR.Results：Seven of 11 tested miRNAs could be detected from serum.Four miRNAs,miR-126,Let-7a,miR141 and miR-21 were identified as metastasis-associated miRNAs.Compared with L-CRC,significant upregulated expression was observed for miR-141 and miR-21 in SLM-CRC and OM-CRC,down-regulated expression was observed for miR-126 in SLM-CRC and OM-CRC,and up-regulated expression of Let-7a in OM-CRC.The receiver operating characteristic （ROC） curve showed serum miR-126 had a cut-off [log10 relative quantity （log10RQ）=--0.2005] with 77.78％ sensitivity and 68.97％ specificity with an area under curve （AUC） of 0.7564,miR-141 had a cut-off （1og10RQ=-0.2285） with 86.11％ sensitivity and 76.11％ specificity with an AUC of 0.8279,and miR-21 had a cut-off （log10RQ=-0.1310） with 73.61％ sensitivity and 66.38％ specificity with an AUC of 0.7479.Conclusions：We identified liver metastasis-associated miRNAs,suggesting serum miR-126,miR-141 and miR-21 may be novel biomarkers for clinical diagnosis of early stage liver-metastatic CRC.

Liver metastasis models of human colorectal carcinoma established in nude mice by orthotopic transplantation and their biologic characteristics

AIM To establish a liver metastasis model of human colorectal carcinoma in nude mice.METHODS Orthotopic transplantation of histologically intact colorectal tissues from patients into colorectal mucosa of nude mice. Tumorgenicity, invasion, metastasis and morphological characteristics of the transplanted tumors were studied by light microscopy, electron microscopy and immunohistochemistry.RESULTS Liver metastasis models of human colon carcinoma (HCA-HMN-1) and human rectal carcinoma (HRA-HMN-2) were established after screening from 34 colorectal carcinomas. They had been passaged in vivo for 18 and 21 generations respectively. There were lymphatic, hemotogenous and implanting metastasesis. CEA secretion was maintained after transplantation. The primary and liver metastatic tumors were similar to the original human carcinoma in histopathological and ultrastructural features, DNA content and chromosomal karyotype.CONCLUSION The liver metastasis models provide useful tools for the study of mechanism of metastasis and its treatment of human colorectal cancer.INTRUDUCTIONSome models of nude mice that fresh human colorectal carcinoma tissue or cells were successfully transplanted subcuteneously have been reported at home and abroad[1,2]. But until now there has been no report on a liver metastasis model of human colorectal carcinoma established by orthotopic transplantation in nude mice in China. Based on our previous models of human liver and pancreas carcinoma by orthotopic transplantation[3,4], we established liver metastasis models of colon and rectum carcinoma with a spontaneous metastasis rate of 100%.

Serological diagnostic factors for liver metastasis in patients with colorectal cancer

AIM:To investigate the serological diagnostic factors for liver metastasis in patients with colorectal cancer.METHODS:One hundred and six adult in-patients with colorectal cancer were studied and divided into patients with liver metastasis(n = 56) and patients without liver metastasis(n = 50).Serum levels of tumor and biochemical markers for liver were measured at the time of diagnosis.RESULTS:The mean survival time was 55.9 mo,36.8 mo and 68.3 mo for the overall patients,patients with liver metastasis and patients without liver metastasis,respectively.Lactate dehydrogenase(LDH) level was significantly correlated with the survival time of colorectal cancer patients.The levels of alanine aminotransferase,aspartate aminotransferase,γ-glutamyltransferase(GGT),LDH and carcinoembryonic antigen(CEA) were significantly higher in patients with liver metastasis than in those without liver metastasis.Patients with lymph node metastasis had a higher risk of liver metastasis than those without lymph node metastasis.The cut points of LDH,GGT and CEA for screening liver metastasis were 180 U/L,30 U/L and 5.0 μg/L,respectively.The sensitivity was 64.3%,69.6% and 70.4%,and the specificity was 64.0%,60.0% and 52.4%,respectively.The sensitivity of parallel test was 85.2% for LDH and CEA,and 92.6% for GGT and CEA,respectively.The specificity of serial test was 85.7% for LDH(or GGT) and CEA.CONCLUSION:Early diagnosis of liver metastasis is of great significance.The sensitivity and specificity of combined tumor and biochemical markers are rather good in screening colorectal liver metastasis.