The Clinicopathological Significance And Relationship Between The Expression Of CIMP And MSI

Background and ObjectivesThe incidence and mortality ofcancer has grudually risen in recent years and became one of the major public health problem in China,especially colorectal cancer(CRC).Due to the concealment of early symptoms,most CRC was found to be late stage of the disease,the patients with poor prognosis.Therefore,find effectivebiomarkers for screening and prognostic is an urgent problem to be solved in clinical.Now,there are three aspectson the molecular pathogenesis mechanism of CRC:chromosomal instability(CIN),microsatellite instability(MSI)and CpG island methylator phenotype(CIMP).Among them,MSI means that the process in which mismatch repair gene mutates during CRC,leading to MMR functional defect and apoptosis disorder,causing tumor to devolop.CIMP mainly refers to the changes caused by abnormal methylation of DNA,such as abnormal activate of protooncogenes and inactivate of tumor suppressor genes,which are related to the occurrence of tumors and some genetic diseases.In order to explore the role of these pathways in the development of CRC,we chose the protein products septin9 and SFRP1 of the CpG island hypermethylation inhibiting genes SEPT9 and SFRP1 in CRC.In addition,MLH1 and MSH2,the protein products of MMR,which were silenced by methylation of gene promoter,were found during MSI.Based on this,we tend to detect the expression of Septin9,SFRP1,MLH1 and MSH2 in normal colonic epithelium,colonic adenomaand CRC tissues and there effects on diagnosis.To improve the effective of clinical services,especially for people in rural or economically underdeveloped areas,reduce the mortality of CRC.Materials and MethodsOne hundred and thirty-eight cases of CRC,Forty-eight cases of high-grade adenoma and Thirty-one cases of low-grade adenoma,were retrospective analysis in the Second Affiliated Hospital of Zhengzhou University from July 2012 to July 2016 and the normal intestinal mucosa adjacent to the adenoma or cancer cell was taken as the internal control.The expression of septin9,SFRP1,MLH1 and MSH2 in the cells were detected by Immunohistochemical methods,and One hundred and thirty-eight cases of CRC patients were followed up.SPSS 25.0 was used for statistical analysis.Results1.The expression of methylation markers in CRC and adenoma:?The negative expression rate of septin9 protein in CRC was 64.49%(89/138),in high-grade adenoma group was 56.25%(27/48),in low-grade adenoma group was 38.71%(12/31).?The negative expression rate of SFRP1 protein in CRCwas 58.68%(81/138),in high-grade adenoma group was 58.33%(28/48),in low-grade adenoma group was 35.48%(11/31).2.The relationship between methylation markers and clinicopathological characteristics of CRC:The negative expressionpatients of septin9 protein were related to the elderly,tumor diameter>5cm and poor tumor differentiation;the negative expression patientsof SFRP1 protein were related to the elderly,tumor diameter>5cm,poor tumor differentiation and high Duke stage.3.The expression of MMR protein in CRC and adenomatous polyps:?The negative expression rate of MLH1 protein in CRC groupwas 13.77%(19/138),in high-grade adenoma group was 10.42%(5/48)andin low-grade adenoma group was6.45%(2/31).?The negative expression rate of MSH2 protein in CRC groupwas 5.80%(8/138),in high-grade adenoma group was 4.17%(2/48)and in low-grade adenoma group was 6.45%(2/31).4.The relationship between the expression of MMR and clinicopathological characteristics of CRC:The negative expressionpatients of MLH1 protein were related to the right colon and mucinous adenocarcinoma,while the negative expressionpatients of MSH2 protein were related to the right colon.5.The relationship between the expression of Septin9,SFRP1,MLH1,MSH2 and the prognosis of CRC patients:The survival rate of the negative expressionpatients of methylation marker septin9 and SFRP1 protein was significantly lower,and there was no significant difference between the negative and positiveexpressionpatientsof MMR protein.6.The relationship between the double negative expression of septin9,SFRP1,MLH1,MSH2 and the prognosis of CRC patients:The survival rateof double negative expression ofseptin9/SFRP 1 was significantly lower than the positive expression group,and there was no significant difference between the double negative expression ofseptin9/MLH1,septin9/MSH2,SFRP1/MLH1,SFRP1/MSH2 and MLH1/MSH2 and the positive expression group.Conclusions1.In the process of colorectal polyps developing to CRC,septin9 and SFRP1 protein can be used as early indicators to predict the canceration of adenomas,and they are positively correlated with the survival rate of CRC.2.The lack of MLH1 and MSH2 protein expression in CRC has no significant effect on the prognosis of patients.