The Study Of Tumor Microenvironment Related Genes Mining And Its Mechanism In HCC

ObjectivePrimary liver cancer is the sixth most commonly diagnosed cancer and the third largest cancer in the world.906000 new cases and 83000 deaths were diagnosed in 2020 alone.Among them,the percentage of HCC was 75%-85%.Tumor microenvironment(TME)is a highly complex ecosystem,which consists of tumor cells,immune cells and stromal cells.The results showed that TME was closely related to the development of HCC.In this study,we will explore the important factors and related genes in the microenvironment of HCC by means of the combination of tumor microenvironment analysis,immune infiltration and weighted network co expression analysis,so as to provide a new perspective for the treatment or diagnosis of HCC.MethodsMethods1.Download HCC transcriptome data from geo(Gene Expression Omnibus)database and TCGA(the Cancer Genome Atlas program),and preprocess the extracted data with Affy package.2.Using estimate package to analyze gene expression data,we estimated the infiltration degree of immune cells,stromal cells and tumor purity;using cibersort,we estimated the infiltration degree of 22 kinds of immune cells in the sample.3.The KM limit product method was used to analyze the infiltration degree of immune cells,stromal cells,tumor purity and 22 kinds of immune cells to screen the clinical features related to the occurrence and development of hepatocellular carcinoma.4.The infiltration degree of immune cells and stromal cells,the purity of tumor and the infiltration degree of 22 kinds of immune cells were taken as clinical information,and the gene network constructed by WGCNA was combined to find out the modules related to tumor microenvironment;using Cytoscape,the hub genes of key modules were screened according to the degree of gene differential expression andconnectivity.5.The survival of hub gene was analyzed by KM limit product method,and the hub gene was verified and analyzed by UALCAN,GEPIA,GSEA and timer.Results1.The analysis of tumor microenvironment showed that the low permeability or low tumor purity of stromal cells was significantly correlated with poor survival and prognosis,and The degree of immune cell penetration in the tumor microenvironment is significantly different between T1 and T3.2.The analysis of immune infiltration showed that low infiltration of inactive mast cells and CD4 + memory T cells was associated with poor survival and prognosis of HCC.3.The abnormal expression of hub gene(AKR1B10,akr1c3,Prdx1,trim16,nfe2l3)in HCC is associated with poor prognosis,and the risk ratio prediction is greater than 1,which can be used as a potential prognostic marker of HCC.4.The expression of nfe2l3 was significantly correlated with stage,and positively correlated with the infiltration of B cells,CD8 + T cells,CD4 + T cells,macrophages,neutrophils and dendritic cells.ConclusionThe infiltration of stromal cells in hepatocellular carcinoma plays an important role in the prognosis of hepatocellular carcinoma.Unactivated mast cells and unactivated CD4 + memory T cells are also potential prognostic factors of hepatocellular carcinoma.AKR1B10,akr1c3,Prdx1,trim16 and nfe2l3 may be potential prognostic markers of hepatocellular carcinoma.Nfe2l3 may play an important role in the dynamic modulation of tumor microenvironment,which needs further study.