Cohort study on the treatment of BRAF V600E mutant metastatic colorectal cancer with integrated Chinese and western medicine

BACKGROUND Patients with BRAF V600E mutant metastatic colorectal cancer(mCRC)have a low incidence rate,poor biological activity,suboptimal response to conventional treatments,and a poor prognosis.In the previous cohort study on mCRC conducted by our team,it was observed that integrated Chinese and Western medicine treatment could significantly prolong the overall survival(OS)of patients with colorectal cancer.Therefore,we further explored the survival benefits in the population with BRAF V600E mutant mCRC.AIM To evaluate the efficacy of integrated Chinese and Western medicine in the treatment of BRAF V600E mutant metastatic colorectal cancer.METHODS A cohort study was conducted on patients with BRAF V600E mutant metastatic colorectal cancer admitted to Xiyuan Hospital of China Academy of Chinese Medical Sciences and Traditional Chinese Medicine Hospital of Xinjiang Uygur Autonomous Region from January 2016 to December 2022.The patients were divided into two cohorts.RESULTS A total of 34 cases were included,with 23 in Chinese-Western medicine cohort(cohort A)and 11 in Western medicine cohort(cohort B).The median overall survival was 19.9 months in cohort A and 14.2 months in cohort B,with a statistically significant difference(P=0.038,hazard ratio=0.46).The 1-3-year survival rates were 95.65%(22/23),39.13%(9/23),and 26.09%(6/23)in cohort A,and 63.64%(7/11),18.18%(2/11),and 9.09%(1/11)in cohort B,respectively.Subgroup analysis showed statistically significant differences in median OS between the two cohorts in the right colon,liver metastasis,chemotherapy,and first-line treatment subgroups(P<0.05).CONCLUSION Integrated Chinese and Western medicine can prolong the survival and reduce the risk of death in patients with BRAF V600E mutant metastatic colorectal cancer,with more pronounced benefits observed in patients with right colon involvement,liver metastasis,combined chemotherapy,and first-line treatment.

Molecular insights into clinical trials for immune checkpoint inhibitors in colorectal cancer:Unravelling challenges and future directions

Colorectal cancer(CRC)is a complex disease with diverse etiologies and clinical outcomes.Despite considerable progress in development of CRC therapeutics,challenges remain regarding the diagnosis and management of advanced stage metastatic CRC(mCRC).In particular,the five-year survival rate is very low since mCRC is currently rarely curable.Over the past decade,cancer treatment has significantly improved with the introduction of cancer immunotherapies,specifically immune checkpoint inhibitors.Therapies aimed at blocking immune checkpoints such as PD-1,PD-L1,and CTLA-4 target inhibitory pathways of the immune system,and thereby enhance anti-tumor immunity.These therapies thus have shown promising results in many clinical trials alone or in combination.The efficacy and safety of immunotherapy,either alone or in combination with CRC,have been investigated in several clinical trials.Clinical trials,including KEYNOTE-164 and CheckMate 142,have led to Food and Drug Administration approval of the PD-1 inhibitors pembrolizumab and nivolumab,respectively,for the treatment of patients with unresectable or metastatic microsatellite instability-high or deficient mismatch repair CRC.Unfortunately,these drugs benefit only a small percentage of patients,with the benefits of immunotherapy remaining elusive for the vast majority of CRC patients.To this end,primary and secondary resistance to immunotherapy remains a significant issue,and further research is necessary to optimize the use of immunotherapy in CRC and identify biomarkers to predict the response.This review provides a comprehensive overview of the clinical trials involving immune checkpoint inhibitors in CRC.The underlying rationale,challenges faced,and potential future steps to improve the prognosis and enhance the likelihood of successful trials in this field are discussed.

Establishing and clinically validating a machine learning model for predicting unplanned reoperation risk in colorectal cancer

BACKGROUND Colorectal cancer significantly impacts global health,with unplanned reoperations post-surgery being key determinants of patient outcomes.Existing predictive models for these reoperations lack precision in integrating complex clinical data.AIM To develop and validate a machine learning model for predicting unplanned reoperation risk in colorectal cancer patients.METHODS Data of patients treated for colorectal cancer(n=2044)at the First Affiliated Hospital of Wenzhou Medical University and Wenzhou Central Hospital from March 2020 to March 2022 were retrospectively collected.Patients were divided into an experimental group(n=60)and a control group(n=1984)according to unplanned reoperation occurrence.Patients were also divided into a training group and a validation group(7:3 ratio).We used three different machine learning methods to screen characteristic variables.A nomogram was created based on multifactor logistic regression,and the model performance was assessed using receiver operating characteristic curve,calibration curve,Hosmer-Lemeshow test,and decision curve analysis.The risk scores of the two groups were calculated and compared to validate the model.RESULTS More patients in the experimental group were≥60 years old,male,and had a history of hypertension,laparotomy,and hypoproteinemia,compared to the control group.Multiple logistic regression analysis confirmed the following as independent risk factors for unplanned reoperation(P<0.05):Prognostic Nutritional Index value,history of laparotomy,hypertension,or stroke,hypoproteinemia,age,tumor-node-metastasis staging,surgical time,gender,and American Society of Anesthesiologists classification.Receiver operating characteristic curve analysis showed that the model had good discrimination and clinical utility.CONCLUSION This study used a machine learning approach to build a model that accurately predicts the risk of postoperative unplanned reoperation in patients with colorectal cancer,which can improve treatment decisions and prognosis.

Clinical Predictors of Cetuximab for First-Line Therapy of Metastatic Colorectal Cancer: A Single Institutional Retrospective Study

Predictive factors of cetuximab efficacy for metastatic colorectal cancer (mCRC) have not been sufficiently revealed. The present study aimed to explore new predictors. A total of 30 patients with KRAS exon 2 wild-type unresectable mCRC, who had been treated with cetuximab-based regimen as first-line therapy, were retrospectively analyzed. We assessed whether gender, age, primary tumor site, RAS genotype, the Eastern Cooperative Oncology Group Performance Status (ECOG PS), metastatic status, histological grade, carcinoembryonic antigen (CEA), treatment regimen, and oxaliplatin-based adjuvant chemotherapy at baseline were associated with cetuximab efficacy. Progression-free survival (PFS) and objective response rate (ORR) were evaluated and statistically analyzed. Analysis of PFS revealed that left-sided tumor and good PS had relevance to good results. PFS among patients with left-sided CRC was longer than that among those with right-sided CRC (median, 10.6 and 3.5 months, respectively). Patients with a PS of 0 - 1 experienced significantly longer PFS than those with a PS of 2 - 3 (median, 8.6 versus 1.3 months, respectively). In analysis of ORR, high histological grade and serum CEA level showed interaction with good effect. Patients with histological grade I/II cancer experienced better ORR than those with histological grade III/IV cancer (76% versus 20%, respectively). ORR among patients with serum CEA level higher than 5.0 ng/ml was significantly higher than that among those with lower serum levels (88% versus 38%, respectively). ECOG PS, tumor location, histological grade, and serum CEA level at baseline might be useful predictors of cetuximab efficacy in the first-line treatment of mCRC.

Traditional Chinese Medicine in colorectal cancer treatment:a bibliometrics study and visualization analysis via CiteSpace

Objective:To evaluate the current state of research and areas of interest for traditional Chinese medicine(TCM)in the field of colorectal cancer treatment.Methods:Related papers published between January 1,2012,and November 27,2021,were found using the Web of Science Core Collection Science Citation Index Expanded.Using CiteSpace's network map generation capability,we then determined the top writers,organizations,countries,keywords,co-cited writers,journals,references,and research trends.Results:This investigation yielded a total of 336 relevant papers.China is the most productive country.Shanghai University of Traditional Chinese Medicine is the leading institution.The journal with the most popularity and publishing volume is Evidence-based Complementary and Alternative Medicine.The author with the most citations and centrality is Lin JM.The terms"epithelial-mesenchymal transition,""cell cycle arrest,""apoptosis,"and"autophagy"are highly frequent and have a high betweenness centrality.Conclusion:According to the results,research on natural products,traditional Chinese medicine(TCM)extracts,and the molecular mechanisms of TCM chemical constituents constitutes the primary focus within TCM cancer treatment investigations.In recent years,there has been a surge of interest in exploring the role of gut microbiota in TCM chemical constituents research,particularly in its ability to induce apoptosis and autophagy in tumor cells,thereby suppressing tumor cell proliferation,metastasis,and invasion.However,due to the intricate composition of TCM and existing technical limitations,the underlying principles guiding TCM's efficacy in treating colorectal cancer remain unclear and warrant further investigation.

Correlation of N-myc downstream-regulated gene 1 expression with clinical outcomes of colorectal cancer patients of different race/ethnicity

AIM： To evaluate the role of N-myc downstream- regulated gene 1 （NDRG1） expression in prognosis and survival of colorectal cancer patients with different ethnic backgrounds. METHODS： Because NDRG1 is a downstream target of p53 and hypoxia inducible factor-1α （HIF-1α）, we examined NDRG1 expression together with p53 and HIF-1α by irnmunohistochernistry. A total of 157 colorectal cancer specimens including 80 from Japanese patients and 77 from US patients were examined. The correlation between protein expression with clinicopathological features and survival after surgery was analyzed. RESULTS： NDRG1 protein was significantly increased in colorectal tumor compared with normal epithelium in both Japanese and US patient groups. Expression of NDRG1 protein was significantly correlated with lymphatic invasion, venous invasion, depth of invasion, histopathological type, and Dukes＇ stage in Japanese colorectal cancer patients. NDRG1 expression was correlated to histopathological type, Dukes＇ stage and HIF-1α expression in US-Caucasian patients but not in US-African American patients. Interestingly, Kaplan-Meier survival analysis demonstrated that NDRG1 expression correlated significantly with poorer survival in US-African American patients but not in other patient groups. However, in p53-positive US cases, NDRG1 positivity correlated significantly with better survival. In addition, NDRG1 expression also correlated significantly with improved survival in US patients with stages Ⅲ and IV tumors without chemotherapy. In Japanese patients with stages Ⅱ and Ⅲ tumors, strong NDRG1 staining in p53- positive tumors correlated significantly with improved survival but negatively in patients without chemotherapy. CONCLUSION： NDRG1 expression was correlated with various clinicopathological features and clinical outcomes in colorectal cancer depending on the race/ethnicity of the patients. NDRG1 may serve as a biological basis for the disparity of clinical outcomes of colorectal cancer patients with different ethnic backgrounds.

Genetic variations in colorectal cancer risk and clinical outcome

Colorectal cancer (CRC) has an apparent hereditary component, as evidenced by the well-characterized genetic syndromes and family history associated with the increased risk of this disease. However, in a large fraction of CRC cases, no known genetic syndrome or family history can be identified, suggesting the presence of &#x0201c;missing heritability&#x0201d; in CRC etiology. The genome-wide association study (GWAS) platform has led to the identification of multiple replicable common genetic variants associated with CRC risk. These newly discovered genetic variations might account for a portion of the missing heritability. Here, we summarize the recent GWASs related to newly identified genetic variants associated with CRC risk and clinical outcome. The findings from these studies suggest that there is a lack of understanding of the mechanism of many single nucleotide polymorphisms (SNPs) that are associated with CRC. In addition, the utility of SNPs as prognostic markers of CRC in clinical settings remains to be further assessed. Finally, the currently validated SNPs explain only a small fraction of total heritability in complex-trait diseases like CRC. Thus, the &#x0201c;missing heritability&#x0201d; still needs to be explored further. Future epidemiological and functional investigations of these variants will add to our understanding of CRC pathogenesis, and may ultimately lead to individualized strategies for prevention and treatment of CRC.

Association of insertion-deletions polymorphisms with colorectal cancer risk and clinical features

AIM To investigate the association between 16 insertiondeletions(INDEL) polymorphisms, colorectal cancer(CRC) risk and clinical features in an admixed population.METHODS O n e h u n d re d a n d fo r ty p a t i e n t s w i t h C R C a n d 140 cancer-free subjects were examined. Genomic DNA was extracted from peripheral blood samples. Polymorphisms and genomic ancestry distribution were assayed by Multiplex-PCR reaction, separated by capillary electrophoresis on the ABI 3130 Genetic Analyzer instrument and analyzed on Gene Mapper ID v3.2. Clinicopathological data were obtained by consulting the patients' clinical charts, intra-operative documentation, and pathology scoring.RESULTS Logistic regression analysis showed that polymorphism variations in IL4 gene was associated with increased CRC risk, while TYMS and UCP2 genes were associated with decreased risk. Reference to anatomical localization of tumor Del allele of NFKB1 and CASP8 were associated with more colon related incidents than rectosigmoid. In relation to the INDEL association with tumor node metastasis(TNM) stage risk, the Ins alleles of ACE, HLAG and TP53(6 bp INDEL) were associated with higher TNM stage. Furthermore, regarding INDEL association with relapse risk, the Ins alleles of ACE, HLAG, and UGT1A1 were associated with early relapse risk, as well as the Del allele of TYMS. Regarding INDEL association with death risk before 10 years, the Ins allele of SGSM3 and UGT1A1 were associated with death risk.CONCLUSION The INDEL variations in ACE, UCP2, TYMS, IL4, NFKB1, CASP8, TP53, HLAG, UGT1A1, and SGSM3 were associated with CRC risk and clinical features in an admixed population. These data suggest that this cancer panel might be useful as a complementary tool for better clinical management, and more studies need to be conducted to confirm these findings.

Clinical laboratory and imaging evidence for effectiveness of agarose-agarose macrobeads containing stem-like cells derived from a mouse renal adenocarcinoma cell population (RMBs) in treatment-resistant, advanced metastatic colorectal cancer:Evaluation of

Objective： The complexity, heterogeneity and capacity of malignant neoplastic cells and tumors for rapid change and evolution suggest that living-cell-based biological-systems approaches to cancer treatment are merited. Testing this hypothesis, the tumor marker, metabolic activity, and overall survival（OS） responses, to the use of one such system, implantable macrobeads [RENCA macrobeads（RMBs）], in phase I and IIa clinical trials in advanced,treatment-resistant metastatic colorectal cancer（m CRC） are described here.Methods： Forty-eight m CRC patients（30 females; 18 males）, who had failed all available, approved treatments,underwent RMB implantation（8 RMB/kg body weight） up to 4 times in phase I and phase IIa open-label trials.Physicals, labs [tumor and inflammation markers, lactate dehydrogenase（LDH）] and positron emission tomography-computed tomography（PET-CT） imaging to measure number/volume and metabolic activity of the tumors were performed pre-and 3-month-post-implantation to evaluate safety and initial efficacy（as defined by biological responses）. PET-CT maximum standard uptake value（SUVmax）（baseline and d 90; SUVmax ≥2.5）, LDH,and carcinoembryonic antigen（CEA） and/or cancer antigen 19-9（CA 19-9） response（baseline, d 30 and/or d 60）were assessed and compared to OS.Results： Responses after implantation were characterized by an at least 20% decrease in CEA and/or CA 19-9 in75% of patients. Fluorodeoxyglucose（FDG）-positive lesions（phase I, 39; 2 a, 82） were detected in 37/48 evaluable patients, with 35% stable volume and stable or decreased SUV（10） plus four with necrosis; 10, increased tumor volume, SUV. LDH levels remained stable and low in Responders（R）（d 0–60, 290.4–333.9）, but increased steadily in Non-responders（NR）（d 0–60, 382.8–1,278.5）（d 60, P=0.050）. Responders to RMBs, indicated by the changes in the above markers, correlated with OS（R mean OS=10.76 months; NR mean OS=4.9 months; P=0.0006）.Conclusions： The correlations of the tumor marker, tumor volume and SUV changes on PET-CT, and LDH levels themselves, and with OS, support the concept of a biological response to RMB implantation and the validity of the biological-systems approach to m CRC. A phase III clinical trial is planned.

Clinical distribution and molecular profiling on postoperative colorectal cancer patients with different traditional Chinese medicine syndromes

Background:Traditional Chinese medicine(TCM)syndrome,also named syndrome,are comprehensive and integral analyses of clinical information which helps to guide different individualized treatment prescriptions.Methods:Thirty healthy controls and 80 colorectal cancer(CRC)patients(including 33 Spleen Qi Deficiency syndrome,23 Dampness Heat syndrome,17 Blood Stasis syndrome and 7 other syndrome)were enrolled into this study.Human mRNAs were extracted from peripheral blood mononuclear cells.The gene expression for CRC patients with different TCM syndrome was determined by microarray and qRT-PCR.Results:Spleen Qi Deficiency,Dampness Heat and Blood Stasis were the most common syndromes in CRC patients.There is a significant difference was found in mRNA expression levels(especially for PIK3CA,STAT3,SOX9 and KDM5C)among Spleen Qi Deficiency,Dampness Heat and Blood Stasis syndrome groups.The higher mRNA levels of JNK1,TP53,MLH1,MSH6,PMS2,SOCS3,TCF7L2,FAM123B,PSAP,FBXW7,SALL4 and the lower expression of inflammatory cytokine IL-6 were found in Spleen Qi Deficiency group but not other syndrome types.The higher mRNA levels of KRAS,MUC16,EGFR,GRASP65,PIK3CA,MAPK7,CD24,STAT3,SLC11A1,Bcl-2,TXNDC17 and some inflammatory cytokines(IL-6,IL-23,TNF-a,CXCR4)were found in Dampness Heat group but not other syndrome types.Blood Stasis syndrome showed higher expression of SOX9,MLH1,MSH6,KDM5C,PCDH11X,PSAP and SALL4,and lower mRNA levels of PIK3CA,CD24,STAT3,CXCR4,TXNDC17 and TP53.The CRC patients with Dampness Heat syndrome might have a poor prognosis than other syndrome types.Conclusion:The identification of syndrome conditions had different impacts on CRC prognosis,and which might be related with different mRNA expression levels.Some oncogenes and pro-inflammatory cytokines were highly expressed in Dampness Heat group but not other syndrome types,suggesting that the CRC patients with Dampness Heat syndrome might have a poor prognosis.Our results prelimitarily uncovered the molecular basis of syndrome differences in CRC prognosis,a better understanding for TCM treatment of CRC.

Clinical features of intracerebral hemorrhage in patients with colorectal cancer and its underlying pathogenesis

BACKGROUND The diagnosis of both cancer and intracerebral hemorrhage(ICH)in the same patient is not uncommon,but the clinical features and pathogenesis of patients with colorectal cancer(CRC)and ICH are still not well known.AIM To investigate the clinical features and underlying pathogenesis of ICH in patients with CRC.METHODS A retrospective review of CRC patients complicated with ICH from three centers between January 2014 and December 2020 was performed.Clinical data such as laboratory examinations,imaging features,prognosis,and underlying pathogenesis were analyzed.RESULTS Of 16673 identified CRC patients,20(0.12%)suffered from ICH.There were 13 males and 7 females,with an average age(mean±SD)of 68.45±10.66 years.Fourteen patients(70%)had distant metastases and most patients(85%)showed an elevation of one or more cancer biomarkers.The hemorrhagic lesions in 13 patients(65%)were in the intracerebral lobe.Four patients were completely dependent and 4 died within 30 days after hemorrhage.Intratumoral hemorrhage(50%)and coagulopathy(50%)accounted for the majority of hemorrhages.CONCLUSION Patients with ICH and CRC often have clinical features with lobar hemorrhage,distant metastases and poor prognosis.Intratumoral hemorrhage and coagulopathy are the main causes of ICH in patients with CRC.

Clinical efficacy and safety of second line and salvage aflibercept for advanced colorectal cancer in Akita prefecture

BACKGROUND Angiogenesis inhibitors(AIs)combination with cytotoxic chemotherapy is a promising treatment for patients with colorectal cancer(CRC).Aflibercept(AFL)is an option for second-line treatment of CRC,according to the‘VELOUR’trial.Currently,we can choose from three AIs,including bevacizumab,ramucirumab,and AFL.Different AIs can be used in subsequent treatment because of their distinctive mechanisms of action.We addressed the uncertainty regarding AFL efficacy and safety in heavily-treated patients by comparing outcomes of survival treatment with second-line treatment.AIM To determine and compare the efficacy and safety profiles of AFL in the secondline and salvage therapy settings.METHODS Clinical data of 41 patients with advanced CRC who received intravenous AFL combined with the folinic acid-fluorouracil-irinotecan(FOLFIRI)regimen were collected retrospectively from six institutions in Japan,for the period from May 2017 to March 2019.Patient characteristics collected included age,sex,tumor location,RAS and RAF status,metastatic sites,number of previous treatment cycles,therapeutic response,adverse events,duration of previous AI treatment,and survival time.The end points were time to AFL treatment failure(aTTF)and median survival time post-AFL(aMST).Statistical analyses were performed to compare the efficacy and safety in the second-line setting with those of the salvage therapy setting,which was defined as the days since the end of secondline therapy.RESULTS All 41 patients who received AFL+FOLFIRI for advanced CRC had metastatic or unresectable cancer.Twenty-two patients received AFL in the second-line setting and nineteen in the salvage therapy setting.The patient characteristics were similar in the two groups,except for two factors.The median duration of the previous AI administration was shorter in the second-line patients compared with that in the salvage therapy patients(144 d vs 323 d,P=0.006).In the second-line and salvage therapy groups,the objective response rates were 11%and 0%,respectively(P=0.50),and the disease control rates were 53%and 50%,respectively(P=1.00).In the second-line and salvage therapy groups,the aTTF(123 d vs 71 d,respectively),aMST(673 d vs 396 d,respectively),and incidence of adverse events of grade 3[8(36%)vs 9(47%)]were not significantly different between the two groups.CONCLUSION AFL can be used to treat advanced CRC patients,with a similar safety and efficacy in the salvage therapy setting as in the second-line setting.

Discussion on the clinical application of colorectal cancer based on the theory of "Tongqixiangqiu"

Objective:To explore the application of the theory of"Tongqixiangqiu"and its application in traditional Chinese medicine in order to find out the clinical application of colorectal cancer.Methods:Referring to the ancient medical works and modern literature on the theory of"Tongqixiangqiu",combined with the disease characteristics of colorectal cancer and the clinical experience of famous doctors in ancient and modern times,to explore its application in the clinical treatment of colorectal cancer.Results:The theory of"Tongqixiangqiu"has rich connotations,among which"anti-adjuvant therapy"and"lung and intestine combined treatment"are the representatives of the specific application of the theory.The methods of cold and heat counteraction,compatibility and external treatment as well as the idea of spleen deficiency and Qi stagnation type colorectal cancer pay attention to tonifying Fei qi,nourishing Fei yin,and promoting Sanjiao Qi mechanism play an important role in the differentiation and treatment of colorectal cancer in TCM.Conclusion:The theory of"Tongqixiangqiu"is widely used in the treatment of colorectal cancer,which has the advantages of significant curative effect,synergism and toxicity reduction,prolonging the survival period and improving the quality of life of patients.

Detection of circulating tumour cells in colorectal cancer:Emerging techniques and clinical implications

Despite several advances in oncological management of colorectal cancer,morbidity and mortality are still high and devastating.The diagnostic evaluation by endoscopy is cumbersome,which is uncomfortable to many.Because of the intra-and inter-tumour heterogeneity and changing tumour dynamics,which is continuous in nature,the diagnostic biopsy and assessment of the pathological sample are difficult and also not adequate.Late manifestation of the disease and delayed diagnosis may lead to relapse or metastases.One of the keys to improving the outcome is early detection of cancer,ease of technology to detect with uniformity,and its therapeutic implications,which are yet to come."Liquid biopsy"is currently the most recent area of interest in oncology,which may provide important tools regarding the characterization of the primary tumour and its metastasis as cancer cells shed into the bloodstream even at the early stages of the disease.By using this approach,clinicians may be able to find out information about the tumour at a given time.Any of the following three types of sampling of biological material can be used in the"liquid biopsy".These are circulating tumour cells(CTCs),circulating tumour DNA,and exosomes.The most commonly studied amongst the three is CTCs.CTCs with their different applications and prognostic value has been found useful in colorectal cancer detection and therapeutics.In this review,we will discuss various markers for CTCs,the core tools/techniques for detection,and also important findings of clinical studies in colorectal cancer and its clinical implications.

Association between triglyceride-glucose index and colorectal polyps:A retrospective cross-sectional study

BACKGROUND Colorectal polyps(CPs)are frequently occurring abnormal growths in the colorectum,and are a primary precursor of colorectal cancer(CRC).The triglyceride-glucose(TyG)index is a novel marker that assesses metabolic health and insulin resistance,and has been linked to gastrointestinal cancers.AIM To investigate the potential association between the TyG index and CPs,as the relation between them has not been documented.METHODS A total of 2537 persons undergoing a routine health physical examination and colonoscopy at The First People's Hospital of Kunshan,Jiangsu Province,China,between January 2020 and December 2022 were included in this retrospective cross-sectional study.After excluding individuals who did not meet the eligibility criteria,descriptive statistics were used to compare characteristics between patients with and without CPs.Logistic regression analyses were conducted to determine the associations between the TyG index and the prevalence of CPs.The TyG index was calculated using the following formula:Ln[triglyceride(mg/dL)×glucose(mg/dL)/2].The presence and types of CPs was determined based on data from colonoscopy reports and pathology reports.RESULTS A nonlinear relation between the TyG index and the prevalence of CPs was identified,and exhibited a curvilinear pattern with a cut-off point of 2.31.A significant association was observed before the turning point,with an odds ratio(95% confidence interval)of 1.70(1.40,2.06),P<0.0001.However,the association between the TyG index and CPs was not significant after the cut-off point,with an odds ratio(95% confidence interval)of 0.57(0.27,1.23),P=0.1521.CONCLUSION Our study revealed a curvilinear association between the TyG index and CPs in Chinese individuals,suggesting its potential utility in developing colonoscopy screening strategies for preventing CRC.

Predicting colorectal cancer prognosis based on long noncoding RNAs of disulfidptosis genes

BACKGROUND A recently hypothesized cause of cell death called disulfidptosis has been linked to the expansion,emigration,and vascular rebuilding of cancer cells.Cancer can be treated by targeting the pathways that trigger cell death.AIM To discover the long non-coding RNA of the disulfidaptosis-related lncRNAs(DRLs),prognosis clinical survival,and treat patients with colorectal cancer with medications.METHODS Initially,we queried the Cancer Genome Atlas database to collect transcriptome,clinical,and genetic mutation data for colorectal cancer(CRC).Training and testing sets for CRC patient transcriptome data were generated randomly.Key long non-coding RNAs(lncRNAs)related to DRLs were then identified and evaluated using a least absolute shrinkage and selection operator procedure,as well as univariate and multivariate Cox regression models.A prognostic model was then created after risk scoring.Also,Immune infiltration analysis,immune checkpoint analysis,and medication susceptibility analysis were used to investigate the causes of the different prognoses between high and low risk groups.Finally,we validated the differential expression and biomarker potential of riskpredictive lncRNAs through induction using both NCM460 and HT-29 cell lines,as well as a disulfidptosis model.RESULTS In this work,eight significant lncRNAs linked to disulfidptosis were found.Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of differentially expressed genes between high-and low-risk groups from the prognostic model showed a close relationship with the immune response as well as significant enrichment in neutrophil extracellular trap formation and the IL-17 signaling pathway.Furthermore,significant immune cell variations between the high-risk and low-risk groups were seen,as well as a higher incidence of immunological escape risk in the high-risk group.Finally,Epirubicin,bortezomib,teniposide,and BMS-754807 were shown to have the lowest sensitivity among the four immunotherapy drugs.CONCLUSION Our findings emphasizes the role of disulfidptosis in regulating tumor development,therapeutic response,and patient survival in CRC patients.For the clinical treatment of CRC,these important LncRNAs could serve as viable therapeutic targets.

Modulation of host N6-methyladenosine modification by gut microbiota in colorectal cancer

As a research hotspot in the field of molecular biology,N6-methyladenosine(m6A)modification has made progress in the treatment of colorectal cancer(CRC),leukemia and other cancers.Numerous studies have demonstrated that the tumour microenvironment(TME)regulates the level of m6A modification in the host and activates a series of complex epigenetic signalling pathways through interactions with CRC cells,thus affecting the progression and prognosis of CRC.However,with the diversity in the composition of TME factors,this action is reci-procal and complex.Encouragingly,some studies have experimentally revealed that the intestinal flora can alter CRC cell proliferation by directly acting on m6A and thereby altering CRC cell proliferation.This review summarizes the data,supporting the idea that the intestinal flora can influence host m6A levels through pathways such as methyl donor metabolism and thus affect the progression of CRC.We also review the role of m6A modification in the diagnosis,treatment,and prognostic assessment of CRC and discuss the current status,limitations,and potential clinical value of m6A modification in this field.We propose that additional in-depth research on m6A alterations in CRC patients and their TME-related targeted therapeutic issues will lead to better therapeutic outcomes for CRC patients.

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.

Effects of postoperative treatment with chemotherapy and cellular immunotherapy on patients with colorectal cancer

BACKGROUND The outcome of surgical treatment for colorectal cancer(CRC)remains unsatis-factory and warrants further exploration and optimization.AIM To clarify the impact of chemotherapy plus cellular immunotherapy[dendritic cell-cytokine-induced killer(DC-CIK)cell immunotherapy]on patients after CRC surgery and to explore the mediating variables.METHODS A total cohort of 121 patients who underwent CRC surgery between January 2019 and April 2022 were selected.The sample comprised a control group of 55 pa-tients who received the XELOX chemotherapy regimen and a research group of 66 patients who received XELOX+DC-CIK immunotherapy.We performed compa-rative analyses of the clinical and pathological data of the two groups,including efficacy(2-year disease-free survival[DFS]rate),the incidence of adverse events(diarrhea,myelosuppression,gastrointestinal reactions,and peripheral neuritis),serum levels of tumor markers[carcinoembryonic antigens and carbohydrate an-tigens(CA)19-9 and CA242],and T-cell subsets[cluster of differentiation(CD)3+,CD3+CD4+,CD3+CD8+,natural killer(NK),and NK T cells].We also conducted preliminary univariate and mul-tivariate analyses of the variables that affected the efficacy of the treatments.RESULTS We found a significantly higher 2-year DFS rate of treatment efficacy in the research group than in the control group,with a statistically lower incidence of adverse events.Both groups showed a reduction in serum tumor markers after treatment but there was no marked intergroup difference.After treatment,the various T-cell subgroup indicators in the control group were significantly lower than those in the research group.The indices of T-cell subsets in the research group showed no significant change from preoperative levels.Univariate analysis revealed a significant correlation between TNM staging,tumor differentiation,and the rates of nonresponse to treatment in CRC patients after surgery.Multivariate results indicated that the treatment approach significantly affected the efficacy of postoperative CRC treatment.CONCLUSION We concluded that XELOX+DC-CIK immunotherapy for postsurgical CRC patients offers reduced rates of treatment-induced adverse events,extended 2-year DFS,enhanced immunity,and increased physiological antitumor responses.

Effectiveness of magnetic resonance imaging and spiral computed tomography in the staging and treatment prognosis of colorectal cancer

BACKGROUND Colorectal cancer(CRC)is a prevalent cancer type in clinical settings;its early signs can be difficult to detect,which often results in late-stage diagnoses in many patients.The early detection and diagnosis of CRC are crucial for improving treatment success and patient survival rates.Recently,imaging techniques have been hypothesized to be essential in managing CRC,with magnetic resonance imaging(MRI)and spiral computed tomography(SCT)playing a significant role in enhancing diagnostic and treatment approaches.AIM To explore the effectiveness of MRI and SCT in the preoperative staging of CRC and the prognosis of laparoscopic treatment.METHODS Ninety-five individuals admitted to Zhongshan Hospital Xiamen University underwent MRI and SCT and were diagnosed with CRC.The precision of MRI and SCT for the presurgical classification of CRC was assessed,and pathological staging was used as a reference.Receiver operating characteristic curves were used to evaluate the diagnostic efficacy of blood volume,blood flow,time to peak,permeability surface,blood reflux constant,volume transfer constant,and extracellular extravascular space volume fraction on the prognosis of patients with CRC.RESULTS Pathological biopsies confirmed the following CRC stages:23,23,32,and 17 at T1,T2,T3,and T4,respectively.There were 39 cases at the N0 stage,22 at N1,34 at N2,44 at M0 stage,and 51 at M1.Using pathological findings as the benchmark,the combined use of MRI and SCT for preoperative TNM staging in patients with CRC demonstrated superior sensitivity,specificity,and accuracy compared with either modality alone,with a statistically significant difference in accuracy(P<0.05).Receiver operating characteristic curve analysis revealed the predictive values for laparoscopic treatment prognosis,as indicated by the areas under the curve for blood volume,blood flow,time to peak,and permeability surface,blood reflux constant,volume transfer constant,and extracellular extravascular space volume fraction were 0.750,0.683,0.772,0.761,0.709,0.719,and 0.910,respectively.The corresponding sensitivity and specificity values were also obtained(P<0.05).CONCLUSION MRI with SCT is effective in the clinical diagnosis of patients with CRC and is worthy of clinical promotion.