Relationship Between RAS,BRAF,HER2 Gene Status And Clinicopathological Features In Colorectal Cancer

Objective To detect the status of KRAS,NRAS,BRAF and HER2 genes in tumor specimens of patients with colorectal cancer(CRC),and to analyze the relationship between gene mutations and clinicopathological features.Methods a total of 116 CRC patients admitted to ordos central Hospital from July2020 to March 2022 were continuously collected.The general data,clinical data and pathological data of the patients were kept intact and fully met the inclusion and exclusion criteria.The common mutation sites of KRAS/NRAS/BRAF gene were detected by fluorescence PCR,and the sequence amplification or significant upregulation of HER2 gene was detected by immunohistochemistry(IHC).Results Among the 116 patients with colorectal cancer confirmed by pathology,36 were female and 80 were male,respectively.There were 58 cases of rectal cancer and colon cancer.The age distribution was between 39 and 89 years old,including 87 patients ≥60 years old and 29 patients < 60 years old.In terms of p TNM staging,there were 10 patients with stage I;There were 24 stage II patients,58 stage III patients,and 24 stageⅣpatients.In terms of the depth of infiltration,there were 3 T1 patients,14 T2 patients,79 T3 patients,and 20 T4 patients.Among them,76 patients had lymph node metastasis and 40 patients had no peripheral lymph node metastasis;There were 115 patients with adenocarcinoma,including 34 cases of highly differentiated adenocarcinoma,61 cases of moderately differentiated adenocarcinoma,20 cases of poorly differentiated adenocarcinoma,including 6 cases of mucinous adenocarcinoma.1 case of signet ring cell carcinoma;No patients with squamous cell carcinoma were found.At least one gene mutation was detected in 65 of 116 patients,including 52 patients with KRAS gene mutation(44.8%),4 patients with NRAS gene mutation(3.45%),11 patients with BRAFV600 E mutation(9.48%),and 2 patients with HER2 positive.The positive rate was 1.72%.There were 3 patients with KARS and NRAS co-mutation,with a common mutation rate of 2.59%,and 1 patient with KRAS and BRAF co-mutation,with a common mutation rate of 0.86%.Among 52 PATIENTS with KRAS mutation,the KRAS mutation rates of patients without and with lymp node metastasis were 30.0% and 52.63%,respectively,which were statistically significant(P=0.02).In the 4 patients with NRAS gene mutation,the mutation was concentrated at codon no.61 Q61 R of exon 3,and no mutation was detected at other sites.NRAS mutations accounted for 1.15% and 10.34% in patients older than or equal to 60 years old and patients younger than 60 years old,respectively,indicating a significant difference in age composition ratio between the two groups(P=0.019).Independent sample T test was used to compare the age characteristics of NRAS mutant and NRAS wild-type patients,and there was a statistical difference in age between the two groups(P=0.023).All patients with BRAFV600 E mutation were adenocarcinomas,and 10 of them were poorly differentiated adenocarcinomas.BRAF mutation rates were 9.20% and 10.34% in patients older than or equal to 60 years old and those younger than 60 years old,respectively.There was a significant difference in age composition ratio between the two groups(P< 0.001).Conclusion(1)KRAS gene mutation is related to lymph node metastasis.Patients with lymph node metastasis have a high mutation rate of KRAS gene.It was not associated with other clinicopathological features(P > 0.05).(2)The mutation of NRAS gene was related to age,and the mutation proportion was higher in patients younger than 60 years old.It was not associated with other clinicopathological features(P > 0.05).(3)The degree of differentiation,depth of invasion and TNM stage of adenocarcinoma were the influencing factors of the MUTATION rate of BRAF gene.The mutation rate of BRAF gene was significantly increased in patients with advanced stage(Ⅳ)and tumor invasion beyond the serous membrane(T4).There was no correlation with other clinicopathological features(P > 0.05).(4)Pathological type and TNM stage were the influencing factors of HER2 overexpression.In patients with advanced stage(Ⅳ)and mucinous adenocarcinoma,HER2 was more likely to be positive.(5)KRAS and NRAS,KRAS and BRAF have common mutations.