Correlation Between Microsatellite Instability And Clinical Molecular Pathological Characteristics Of Colorectal Cancer

Background:Colorectal cancer(CRC)is one of the common malignant tumors in the world.In recent years,with the rapid economic development and the continuous improvement of people’s living standards,great changes have taken place in the lifestyle,leading to the steady rise of its incidence.CRC is largely considered to be a heterogeneous disease,with different molecular subtypes showing different behavior not only in terms of overall prognosis,but also potentially in terms of response to adjuvant chemotherapy.Microsatellite instability(MSI),KRAS and BRAF gene mutations have become an important part of the evaluation of patients with colorectal cancer.The detection strategies and clinical significance of these genes at specific stages are not clear.Therefore,it is important to further clarify the relationship between each molecular biomarker and clinicopathological characteristics of CRC patients.Objective:1.To investigate the relationship between MSI,KRAS and BRAF gene status and clinicopathological characteristics of colorectal cancer.2.To explore the correlation and clinical significance between MSI,KRAS and BRAF gene states.3.To investigate the correlation and clinical significance between KRAS and BRAF gene status in colorectal cancer.Method:320 cases of paraffin specimens of colorectal cancer who were resected and diagnosed in the First Affiliated Hospital of Yangtze University from January 2018 to November 2020 were collected.The relevant case data of the patients were collected in the medical record room of our hospital,including the corresponding clinical data of the patients and the results of postoperative KRAS and BRAF gene testing.The expression of MMR protein(MLH1,MSH2,MSH6 and PMS2)was detected by immunohistochemistry.All data were analyzed using SPSS 21.0 statistical software.Result:1.The incidence of MSI-H was 11.3%;In the MSI-H group,the tumor volume was larger,the proportion of right colon was more,the degree of tumor differentiation was lower,the lymph node metastasis was rare,and the serum CEA was more in the normal range,the difference was statistically significant(P<0.05).MMR status was not related to gender,onset age,gross type,tissue type,depth of invasion(T),TNM stage,preoperative serum CA199 level and other clinicopathological characteristics.2.KRAS gene mutation was significantly higher in mucinous adenocarcinoma than in adenocarcinoma tissues,and the difference was statistically significant(P=0.014).KRAS gene mutation group was prone to lymphatic metastasis,and the difference was statistically significant(P=0.000).KRAS gene mutation was more likely to occur in advanced colorectal cancer,and the difference was statistically significant(P=0.000).The level of CA199 in the KRAS mutation group was significantly higher than that in the wild group,and the difference was statistically significant(P=0.018).KRAS gene mutation was not related to the clinicopathological characteristics such as gender,age,tumor size,tumor location,gross classification,degree of differentiation,depth of invasion(T),preoperative serum CEA level.3.BRAF gene mutations in the poorly differentiated group were significantly higher than those in the highly and moderately differentiated groups,and the difference was statistically significant(P=0.003).BRAF gene mutation was not correlated with gender,age,tumor size,tumor location,gross classification,tissue type,depth of invasion(T),lymph node metastasis,TNM stage,preoperative serum CEA and CA199 levels.4.The mutation rate of KRAS gene in MSI-H group was 25%(9/36),which was significantly lower than that in MSS/MSI-L group(45.4%)(129/284).KRAS gene mutation was positively correlated with MSS/MSI-L,and the difference was statistically significant(rs=0.130,P=0.020).5.The mutation rate of BRAF gene in MSI-H group was 19.4%(7/36),significantly higher than 2.1%(6/284)in MSS/MSI-L group.BRAF gene mutation was negatively correlated with MSS/MSI-L,and the difference was statistically significant(P=0.000,r_s=-0.277).6.The total mutation rate of KRAS gene was 43.1%(183/320).The total mutation rate of BRAF was 4.1%(13/320).KRAS mutation was negatively correlated with BRAF mutation,and the difference was statistically significant(P=0.001,r_s=-0.179).Conclusion:1.The incidence of MSI-H in CRC was 11.3%.Different MMR states have unique clinicopathological characteristics in CRC.In the MSI-H group,the tumor volume was larger,the proportion of the right colon was more,the degree of tumor differentiation was lower,lymph node metastasis was rare,and the serum CEA was more in the normal range.2.The total mutation rate of KRAS gene was 43.1%;KRAS gene mutation is related to tissue type,lymph node metastasis,TNM stage,CA199 level and other pathological characteristics.Patients with KRAS gene mutation are prone to lymph node metastasis,mostly in late stage,mainly mucinous adenocarcinoma,and preoperative serum CA199level is prone to increase.Mutations in the KRAS gene are more common in MSS/MSI-L.3.The total mutation rate of BRAF gene was 4.1%;BRAF gene mutation was mainly found in patients with poorly differentiated colorectal cancer.BRAF mutations are more common in MSI-H.4.KRAS mutation and BRAF mutation are mutually exclusive.