Bioinformatics analysis to screen and identify key biomarkers of papillary renal cell carcinoma

Abstract Background: Papillary renal cell carcinoma (PRCC) is the second most common type of renal cell carcinoma after clear cell renal cell carcinoma(ccRCC). Its pathological classification is controversial and its molecular mechanism is poorly understood. Therefore, the identification of key genes and their biological pathways is of great significance to elucidate the molecular mechanisms of PRCC occurrence and progression. Methods:Downloaded PRCC-related datasets GSE7023, GSE48352 and GSE15641 from the Gene Expression Omnibus (GEO) database. Differential expression genes (DEG) were identified and gene ontology (GO) term enrichment analysis and Kyoto Encyclopedia of Genes and Genomics (KEGG) pathway analysis were performed. Cytoscape and STRING are used to construct the Protein-Protein Interaction Network (PPI) and module analysis to find hub genes and key pathways. Hierarchical clustering of hub genes was constructed using UCSC. Overall survival and relapse-free survival of Hub genes were analyzed using Kaplan-Meier plotter. UALCAN was applied to analyze genes expression in primary organizations, different stages ,different subtypes and races.Results: A total of 214 DEG genes were identified, including 205 down-regulated genes and 9 up-regulated genes. DEG is mainly concentrated in angiogenesis, kidney development, oxidation-reduction process, metabolic pathways, etc. 17 hub gene enrichment mainly in angiogenesis, cell adhesion, platelet degranulation, Leukocyte transendothelial migration biological processes, etc. 17 hub genes were screened out, which were mainly enriched in the biological processes of angiogenesis, cell adhesion, platelet degranulation, and leukocyte transendothelial migration. Survival analysis showed that EGF, KDR, CXCL12, REN, PECAM1, CDH5, THY1, WT1, PLAU and DCN may be related to the carcinogenesis, metastasis or recurrence of PRCC. Conclusions: DEG and hub genes identified in present study provide clues to the specific molecular mechanisms of PRCC occurrence and development, and may be potential molecular markers and therapeutic targets for accurate classification and efficient diagnosis and treatment of PRCC.