Relationship Between Colorectal Cancer-related Gene Mutations And Clinicopathological Features And Progression-free Survival

Objective:To explore the related gene mutations and clinicopathological features of patients with colorectal cancer and to analyze their progression-free survival(PFS)in order to provide some help for more effective prevention,diagnosis,treatment and prognosis of colorectal cancer.Methods:A total of 71 patients with colorectal cancer who underwent surgery in the third clinical hospital of Jilin University of Jilin University from September 2018 to October 2021 with complete medical records and successful gene detection were selected as subjects.The clinical data and tumor histological samples of these patients were collected.Colorectal cancer-related genes on the Illumina Hiseq/Mi Seq Dx high-throughput sequencing platform.By chi-square test and ROC curve,SPSS21.0 software was used to explore the relationship between 12 genes closely related to colorectal cancer,such as APC,KRAS,BRAF,PIK3 CA,SMAD4,p53,etc.,and the clinicopathological features such as sex,age,tumor location,TNM stage,nerve invasion and vascular invasion.By means of Kaplan-Meier univariate analysis,Log-rank test and COX multivariate regression,the SPSS21.0 software was used to analyze the clinical characteristics of 45 colorectal cancer patients with complete survival data and standardized first-line treatment,and the relationship between key gene mutations such as APC,KRAS,BRAF,PIK3 CA,SMAD4,p53 and PFS.Results:1.Of the 71 patients with colorectal cancer,(1)45(63.4%)were male and 26(36.6%)were female;37(52.1%)were ≥ 60 years old,34(47.9%)were less than 60 years old;(2)54(76.1%)were left colon,17(23.9%)were right colon;(3)20(28.2%)were stage Ⅰ-Ⅱ and 51(71.8%)were stage Ⅲ-IV.(4)There were 20 patients with liver metastasis;7 patients with lung metastasis,50 patients with celiac lymph node metastasis,40 patients with vascular tumor thrombus,30 patients with nerve invasion;(5)14patients with family history;(6)In addition,the survival information of 45 patients of 71 patients with colorectal cancer were collected.2.There is an obvious causal relationship between different gene mutations and sex and age of the patients: TP53 gene mutations were more likely to occur in males and XRCC1 gene mutations were more likely to occur in females(P<0.05).The rate of TP53 mutation was higher in people aged ≥ 60 years old(P<0.05).3.There are significant differences between different gene mutations and the location of the disease: The gene mutations of PIK3 CA,TOP1 and MLH1 in the right colon were higher than those in the left colon(P<0.05).4.The mutation rate of DPYD gene in T4 stage was higher than that in T3 stage(P<0.05).5.There were significant differences between different gene mutations and vascular and nerve in patients: Patients with APC and TP53 gene mutations were more likely to develop vascular tumor thrombus(P<0.05).Patients with TP53 gene mutations were also more likely to have nerve invasion(P<0.05).6.Patients with APC and TP53 gene mutations were more likely to have liver metastasis(P<0.05).This is further confirmed by the ROC curve of APC and TP53 genes.No significant difference was found between colorectal cancer patients with KARS,BRAF,PIK3 CA,SMAD4 gene mutations and liver and lung metastasis(P>0.05).7.There were significant differences between different gene mutations and progression-free survival: colorectal cancer patients with KRAS and APC gene mutations had shorter PFS than those with wild types of KRAS and APC genes(P<0.05).The PFS of colorectal cancer patients without liver metastasis was significantly longer than that of colorectal cancer patients without liver metastasis(P<0.05).8.Multivariate analysis of Cox regression model showed that KRAS gene(HR:36.767,CI:2.636-512.812,P<0.05)and APC gene(HR:21.311,CI:0.995-456.558,P<0.05)were independent risk factors for PFS shortening in patients with colorectal cancer.SMAD4,P53,BRAF,PIK3 CA and other genes and clinical features were not significantly different from PFS in patients with colorectal cancer(P>0.05).Conclusion:1.TP53 gene mutation is easy to occur in male,XRCC1 gene mutation is more likely to occur in female;the mutation rate of TP53 gene in people aged ≥60 years old is higher than that in people <60 years old;the mutation rate of PIK3 CA,MLH1,TOP1 gene in right colon cancer is higher than that in left colon cancer,and the mutation rate of DPYD gene in T4 stage is higher than that in T3 stage.2.Colorectal cancer patients with vascular tumor thrombus invasion are more likely to have APC and TP53 gene mutations;colorectal cancer patients with nerve invasion are more likely to have TP53 gene mutations;colorectal cancer patients with APC and TP53 gene mutations are more likely to have liver metastasis.3.The PFS of colorectal cancer patients with KRAS and APC gene mutations was significantly lower than that of KRAS and APC gene wild type colorectal cancer patients,and KRAS and APC gene mutations were independent risk factors for PFS shortening in colorectal cancer patients.