Identification of Biomarkers for Prognosis and Immunotherapy in Clear Cell Renal Cell Carcinoma

Abstract Background: Clear cell renal cell carcinoma (ccRCC) is the dominating subtype of renal cancer with high malignancy and poor prognosis, accounts for the majority of kidney cancer deaths. We conducted this research to identify novel potential biomarkers for the prognosis and immunotherapy of ccRCC patients. We screened out differentially expressed genes (DEGs) between ccRCC tissues and adjacent normal tissues with 4 microarray series from GEO database and took function analysis of DEGs with GO and KEGG pathway. Then, we constructed PPI network and identified target genes with prognostic value in ccRCC, performed immunological correlation analysis of the candidate genes to seek potential biomarkers of immunotherapy in ccRCC. Results: In total, 159 up-regulated genes and 223 down-regulated genes were screened out and 11 genes including TIMP1, PCK1, HMGCS2, G6PC, FBP1, ACAA1, HADH, HAO2, TGFBI, RRM2 and SUCLG1 were found to be associated with prognoses of ccRCC patients. After further screening and verification of the mRNA and protein expression, down-regulation of PCK1, HMGCS2, and up-regulation of RRM2 were significantly correlated with poorer prognoses both in overall survival and disease free survival in ccRCC. Further immunological correlation analysis showed RRM2 expression was correlated with immune infiltration and immunological checkpoint in ccRCC.Conclusion: We identified PCK1, HMGCS2 and RRM2 as potential markers for the prognosis of ccRCC patients with bioinformatic analyses. RRM2 may plays an important role in the oncogenicity of ccRCC and is a potential target for immunotherapy of ccRCC patients.