Exploring The Impact Of Gene Mutation On The Progression Of Multistage Colorectal Cancer

Objective: To investigate the somatic cell gene mutations in the progression of colorectal cancer from benign adenoma to more aggressive mucinous adenocarcinoma and to analyze the relationship between the gene mutation and tumor progression.Moreover,the article explains the reasons for the differences in the prognosis of the left-sided and right-sided colon cancer by comparing the number of mutations in the cases.Methods: In this study,tumor specimens from patients with different stages and different states of co-occurring colonic adenoma,colonic adenocarcinoma,and colonic mucinous adenocarcinoma and 23 sporadic colorectal cancer patients were extracted and analyzed for gene mutation that targeted domain capture highdepth sequencing was performed on 1021 coding regions of 70 genes in different tumor development stages during the progressive evolution from normal tissue to mucinous adenocarcinoma by high-throughput gene sequencing platform.Result: About two patients with multiple primary colorectal cancer,case 1showed an increasing trend in the number of somatic gene mutations and the mutation overlap rate of each sample from normal tissue to mucinous adenocarcinoma(11.76% from normal tissue to adenoma tissue,25% from adenoma tissue to adenocarcinoma tissue(T3),and 27.06% from adenocarcinoma tissue to mucinous adenocarcinoma tissue(T3)),cases 2 of patients with lynch syndrome,its normal tissue ascending colon adenomas sigmoid colon mucous adenocarcinoma tissue(T2)ascending colon mucous adenocarcinoma tissue as a(T4)and tumor tissue development,gene mutation number increasing trend,but we found that its each sample somatic mutations present no significant overlap.There were APC gene mutations in the normal tissues and the three pathological tissues of case 1,but only KRAS TP53 gene mutations in the mucinous adenocarcinoma tissues of Case 2.The number of somatic gene mutations in the mucinous adenocarcinoma tissues of ascending colon(T4)was 120,and the number of mutations in the mucinous adenocarcinoma cells of sigmoid colon(T2)was 93.However,the number of gene mutations in the normal tissue of the left and right colon was exactly the same.The number of gene mutations in the right colon adenocarcinoma was less than that in the left mucinous adenocarcinoma in case 1.In a cohort of 23 patients with single colorectal cancer,the number of gene mutations in the mucinous adenocarcinoma group was higher than the adenocarcinoma group(P<0.05);the number of gene mutations in T4 group was higher than that in T2-3 group(P<0.05);the number of gene mutations in M1 group was higher than that in M0 group(P<0.05);but the T stage in M1 group was also higher than that in M0 group(P<0.05).The 23 cases of colorectal cancer patients were grouped according to the malignant degree of tumor(adenocarcinoma group 20: mucinous adenocarcinoma group 3),and it was found that 3 cases of adenocarcinoma group did not have TP53 gene mutation,6 cases of mucinous adenocarcinoma group did not have APC mutation,all had KRAS mutation,and only case 1 had TP53 mutation.The 23 cases with colorectal cancer were grouped by left and right colon,and the right colon cancer patients had more gene mutations(P<0.05),there was no significant relationship between T stage and left and right semicolon carcinoma(P>0.05),but the tumor volume of the right colon cancer was larger than that of the left(P<0.05),which suggests that the right colon cancer patients with a longer tumor doubling time.In order to further verify the difference of T stage in the diagnosis of left and right hemicolon carcinoma,about 2400 patients with left and right hemicolon carcinoma in our research center were recruited for comparison.The results showed that the right hemicolon carcinoma patients had higher T stage than the left hemicolon(P<0.001).Conclusion: Cumulative gene mutations were found in the time-dominated development of colorectal cancer with tumor multiplication,T stage increase and invasion ability enhancement.At present,the differences between right and left colon cancer are also associated with longer tumor growth time,increased tumor invasion ability and more cumulative gene mutations at the time of diagnosis of right colon cancer,which may be the cause of poor prognosis of right colon cancer.