Construction Of Cancer Prognosis Model Based On KRAS Mutation-Related Genes

KRAS mutations are common in patients with pancreatic and lung cancer,and are associated with prognosis,immune response,or immunotherapy.In order to study the effect of KRAS mutation on tumor immune microenvironment and to construct the prognosis model based on KRAS mutation-related genes,we downloaded the genetic data and clinical data of patients with pancreatic ductal adenocarcinoma(PDAC)and lung adenocarcinoma from TCGA and GEO databases.Based on this,the differences in gene expression between KRAS mutation and wild-type patients were analyzed,and the differentially expressed genes(DEGs)were analyzed by univariate Cox analysis.According to the selected prognostic DEGs,the prognostic model was constructed by LASSO Cox regression,and the influence of the prognostic model on tumor immune microenvironment and immunotherapy was analyzed in detail.In PDAC,25 immune-related DEGs related to prognosis were found,and an immuno-prognostic model containing 5 genes was constructed.The model can effectively classify PDAC patients into high risk and low risk groups in TCGA training set and GEO validation set.Multivariate Cox regression analysis found that risk score was an independent prognostic factor in patients with PDAC.In addition,compared with the high-risk group,patients in the low-risk group had high expression of tumor infiltrating CD4~+T cells,neutrophils,macrophages and dendritic cells and immune checkpoint molecules,such as PD1,CTLA4,TIM3,TIGIT and LAG3.Finally,a nomogram was constructed based on risk score,tumor size,tumor location,and whether to receive chemotherapy to better predict 1-,2-and 3-year PDAC survival.In lung adenocarcinoma,220 DEGs related to KRAS mutation were found,and a prognostic model containing 12 genes was constructed.This model can effectively classify patients with lung adenocarcinoma into high risk and low risk groups in TCGA training set and GEO validation set.Multivariate Cox regression analysis found that risk score was an independent prognostic factor for patients with lung adenocarcinoma.In addition,patients in the low-risk group had more tumor-infiltrating B cells,CD4~+T cells,CD8~+T cells,macrophages,and dendritic cells than those in the high-risk group,and were more likely to benefit from immunotherapy,but less sensitive to chemotherapy drugs.Finally,a nomogram was constructed based on risk score,tumor stage,tumor T stage,and tumor N stage to better predict the survival rates of patients with lung adenocarcinoma at 1-,3-and 5-years.This study provides new insights into the immune microenvironment and cancer treatment of PDAC and lung cancer.The constructed model can divide patients with PDAC and lung adenocarcinoma into subgroups with different prognosis and immunophenotype,which has potential clinical application value and provides reference for the implementation of personalized medicine and improvement of patient prognosis in the future.