Screening Of Microenvironment-related Genes With Prognostic Value In Clear Cell Renal Cell Carcinoma

Background:Clear cell renal cell carcinoma(ccRCC)is the most common type with poor prognosis in kidney tumor.with the development of the times and the advancement of contemporary high-throughput sequencing technology,there is a deeper understanding of ccRCC at the molecular level.However,the mechanism of tumorigenesis,progression and metastasis remains unclear and there is a lack of effective biomarkers.In recent decades,more and more studies have shown that the interaction between tumor cells and the microenvironment has an important impact on prognosis.The tumor microenvironment(TME)is a complex array of cells and extracellular matrix(ECM)proteins that tumor cells construct during the course of multistep tumorigenesis.Immune and stromal cells are two vital components of the tumor microenvironment.By combining these two main components to analyze the tumor microenvironment,to find new target gene sites and to screen new molecular markers that can judge the prognosis,it could be helpful to provide new research ideas for exploring the occurrence and development of cancer and provide the basis for the development of new targeted drugs.Objective:Our study aims to better understand and probe genes with prognostic value that are closely related to the tumor microenvironment,and to discuss the relevant proteins or pathways.Methods:According to immune/stromal scores calculated by the ESTIMATE algorithm,we divided ccRCC patients from The Cancer Genome Atlas(TCGA)database into low and high score groups.We explored the relationship between immune/stromal scores and WHO/ISUP(World Health Organization/International Society of Urological Pathology)grading and overall survival,separately.Then we identified the genes which were differentially expressed between low and high score groups and significantly associated with overall survival.Enrichment analysis and protein-protein interaction network were performed for these genes.Finally,another independent cohort from the International Cancer Genome Consortium(ICGC)database was used to validate these genes.Results:We acquired 243 differentially expressed genes which were significantly associated with overall survival.The result of functional enrichment analysis and protein-protein interaction network indicated that these genes mainly be involved in extracellular matrix and regulation of cellular transmembrane activities.13 genes were confirmed with prognostic value in ICGC database.Conclusion:Our study excavated 13 genes with prognostic value which were related with tumor microenvironment.Further study of these genes may be of great significance for prognosis and potential treatment options for ccRCC patients.