Clinicopathological Characteristics And Prognostic Value Of KRAS,NRAS And BRAF Mutations In Colorectal Cancer

Objective:To assess the latest clinicopathological features and prognostic value of KRAS,NRAS and BRAF gene mutation status,and to provide a theoretical basis for genetic testing strategies for colorectal cancer patients.Methods:A database of patients who underwent surgical treatment at the Department of Colorectal Surgery,Second Hospital of Jilin University between January 1,2017 and December 1,2020 was retrospectively analyzed.Clinical information including gender,age,pathological immunohistochemical results,tumor histology,lymphovascular infiltration,tumor location,tumor size,degree of differentiation,tumor staging,tumor TNM stage,and surgical modality were collected.Our pathologists assessed the pathological features and clinical staging based on the TNM tumor staging criteria of UICC/AJCC 8th edition.The mutation status of KRAS gene,BRAF gene and NRAS mutation was detected based on mutation blocking amplification system PCR(ARMS-PCR)technology at the Precision Medicine Center of Second Hospital of Jilin University.The clinicopathological characteristics of KRAS,NRAS and BRAF gene mutations and the prognostic value were analyzed.Results:(1).KRAS mutations accounted for 40.2%(68/169)of all colorectal cancer patients,with relatively high mutation rates in exon 2in G12D(15.4%),G12V(9.4%)and G13D(8.8%).the BRAF V600 E mutation rate was 4.7%(8/169).(2).Clinicopathological correlation analysis showed that patients with KRAS mutations had a higher proportion of perinerural invasion and mucinous adenocarcinomas compared with KRAS wild-type patients(P<0.05).There was no difference in clinicopathological characteristics between KRAS mutation subtypes G12 D,G12V,and G13 D.(3).There was no significant correlation between NRAS and clinicopathological features.(4).BRAF mutation was associated with right hemi colon cancer with higher proportion of N-stage and higher proportion of vascular infiltration(P<0.05).(5).Prognostic analysis showed that colorectal cancer patients with KRAS gene mutation had worse prognosis(P<0.005).(6).Multivariate Cox regression analysis showed that KRAS mutation,patient gender,and patient age size and tumor site were independent prognostic factors for the prognosis of colorectal cancer patients(P<0.05).Conclusions:(1)The mutation type rate of KRAS gene was 40.2%,and the mutation rate of BRAF and NRAS was 4.7%.(2)Among the KRAS mutated loci,the relatively high mutation rates were G12D(15.4%),G12V(9.4%)and G13D(8.8%).(3)Among the NRAS mutation sites,the highest mutation rate(2.2%)was found in Q61 R on exon 3.(4)Perineural invasion and mucinous adenocarcinoma were significantly associated with KRAS mutation rate.No significant correlation was found between NRAS and clinicopathological features.(5)Survival analysis showed that KRAS was a poor prognostic factor for CRC patients.Gender,age,tumor site,KRAS status were independent risk factors associated with patient prognosis.