Association Of KRAS Gene And Microsatellite Instability With Clinicopathological Features And Prognosis In Colon Cancer Patients

Objective:With development of medical technology,more and more molecular markers and genetic locus have been found.They were associated with the clinicopathological characteristics of patients and had partial impact on prognosis.Kirsten rat sarcoma viral oncogene(KRAS),v-raf murinesar-coma viral oncogene homolog B1(BRAF)and microsatellite instability(MSI)has been proved to be related to the treatment and prognosis of colon cancer patients.This study retrospectively analyzed the relationship between KRAS gene mutation and MSI status and the clinicopathological characteristics of colon cancer patients.The objective was to investigate the effect of KRAS gene mutation and MSI status on prognosis of colon cancer patients and to analyze the independent prognosis factors.Methods:A retrospective analysis was performed on patients with colon cancer who underwent surgical treatment in the Affiliated Hospital of Qingdao University from August 2015 to November 2018 and received standardized treatment in the oncology department of our hospital after surgery.The clinical data of patients were collected and inclusion and exclusion criteria were formulated.The end point of the study was overall survival(OS).The follow-up date was until June 2021.Death is regarded as the clinical outcome.The KRAS gene mutation was detected by polymerase chain reaction(PCR)and the positive status of mismatch repair proteins(MLH1,PMS2,MSH2,MSH6)in the tumor tissues of colon cancer patients was detected by immunohistochemistry.Theχ~2 test was used to compare the relationship between KRAS gene mutation and MSI status and the clinicopathological characteristics of colon cancer patients.Multivariate logistic regression analysis was used to analyze the risk factors affecting KRAS gene mutation and MSI status.The survival rate was calculated by life table method.Kaplan-meier method was used for survival analysis and Log-rank test was used to compare survival curves.Cox proportional risk model was used to compare overall survival and to analyze the independent prognosis factors.Results:A total of 1127 colon cancer patients were collected.There were 405 KRAS mutant patients(35.9%)and 96 MSI-H patients(8.5%)of the total.According to the established inclusion and exclusion criteria,a total of 372 patients were included in the study.The median follow-up time was 50 months and the loss to follow-up rate was 6.06%(24/396).The results showed that KRAS gene mutation in age(P=0.021),tumor location(P=0.020),pathological type(P=0.003)and number of dissected lymph nodes(P=0.004)was significantly different.Age(OR=0.554,95%CI:0.350～0.877,P=0.012),MSI status(OR=0.557,95%CI:0.313～0.993,P=0.047),pathological type(OR=1.918,95%CI:1.136～3.239,P=0.015)were independent risk factors affecting KRAS gene mutation.The results showed that MSI status in age(P=0.003),preoperative CEA(P=0.003),tumor site(P<0.001),pathological type(P<0.001),degree of differentiation(P<0.001),tumor size(P<0.001),T stage(P<0.001)and N stage(P=0.005)was significantly different.Age(OR=0.390,95%CI:0.197～0.772,P=0.007),preoperative CEA(OR=0.241,95%CI:0.125～0.466,P<0.001),tumor site(OR=4.787,95%CI:2.321～9.871,P<0.001),pathological type(OR=3.445,95%CI:1.752～6.773,P<0.001),differentiation degree(OR=3.145,95%CI:1.613～6.133,P=0.001)and T stage(OR=7.358,95%CI:3.353～16.150,P<0.001)were independent risk factors affecting MSI status.Cox regression analysis showed that age(HR=1.530,95%CI:1.001～2.295,P=0.037),BMI(HR=1.516,95%CI:1.001～2.295,P=0.049),tumor site(HR=2.326,95%CI:1.527～3.542,P<0.001),KRAS gene mutation(HR=1.800,95%CI:1.205～2.687,P=0.004),MSI status(HR=0.231,95%CI:0.116～0.461,P<0.001),degree of differentiation(HR=1.731,95%CI:1.122～2.670,P=0.013)and N stage(HR=1.808,95%CI:1.203～2.717,P=0.004)were independent prognosis factors of colon cancer patients.Conclusion:Both KRAS mutant and MSI-H colon cancer patients have unique clinicopathological characteristics.They are also independent prognosis factors of colon cancer patients.KRAS gene mutation suggests a poor prognosis.MSI-H predicts better clinical outcome in stage II and III colon cancer patients.Both KRAS gene mutation and MSI status can provide basis for the selection of targeted and immune drugs.