Differences in gene mutation profiles of colon cancer patients with or without a KRAS mutation

Abstract

RAS plays an important role in the carcinogenesis of colorectal epithelial cells, but RAS mutations are only present, at most, in approximately 50% of patients. In order to compare the gene mutation profiles of patients with or without a KRAS mutation, the clinicopathological data of 858 patients and NGS test results of 1697 patients with colorectal cancer were used in this analysis. In 858 patients, the mutation rate of KRAS was 50.8% (i.e., 436/858). Only 2 out of 349 (0.5%) KRAS mutant patients had a BRAF mutation, while 25 out of 422 (5.9%) KRAS wild-type patients had a BRAF mutation (p < 0.0001). The median OS of patients with a mutant or wild-type KRAS were 83.47 months and not reached, respectively (HR: 0.8147; 95% CI: 0.6271–1.051; p = 0.1153). The NGS results showed that in RAS mutant patients, genes with a high mutation rate mainly included APC, TP53, PIK3CA, Smad4, and Fbxw7, and in RAS wild-type patients, genes with a high mutation rate mainly included TP53, APC, LRP1B, MYC, and BRAF. The mutation rates of BRAF and EGFR in the RAS wild-type group were 15% and 9%, respectively, while they were only 3% in the RAS mutant group. The mutation rate of PIK3CA in the RAS mutant group was 31%, while that in the RAS wild-type group was 14%. The mutation rate of APC was 72.2% (i.e., 687/952). The mutation rate of the gene, RNF43, in the APC wild-type group was 5.23 times higher than that in the APC mutant group, and the gene, NSD1, in the APC wild-type group was 0.07 times higher than that in the APC mutant group. The mutation rate of TP53 was 78.2% (i.e., 744/952). The mutation rate of MLH1 in the TP53 wild-type group was 8.42 times higher than that in the TP53 mutant group, which was significantly higher than that in the TP53 mutant group. Generally, the gene mutation profiles were significantly different between KRAS mutation and wild-type colorectal cancer patients. A single gene mutation may be sufficient to cause the dysfunction of a signal transduction pathway, and APC, TP53, or RAS are not necessary for the carcinogenesis of sporadic colorectal cancer.