SKA3 Serves as a Biomarker for Poor Prognosis in Kidney Renal Papillary Cell Carcinoma
Dechao Feng, Facai Zhang, Ling Liu, Qiao Xiong, Hang Xu, Wuran Wei, Zhenghua Liu, Lu Yang
Abstract
Background: There is a surprising paucity of studies investigating the potential mechanism of SKA3 in the progression and prognosis of kidney renal papillary cell carcinoma (KIRP). Methods: We used TCGA and other databases to analyze the expression, clinical value, and potential mechanisms of SKA3 in KIRP patients. We also explored therapeutic agents for KIRP through GSCALite. Results: SKA3 mRNA expression was significantly upregulated and the area under the curve was 0.792 (95% CI 0.727– 0.856). Increased SKA3 expression was related to shorter overall survival, disease-specific survival and progression-free survival. Hub genes in protein–protein interactions were CDK1 , CDC20 , CCNB1 , CCNA2 , BUB1 , AURKB , BUB1B , PLK1 , CCNB2 , and MAD2L1 , which were differentially expressed and also associated with KIRP prognosis. Gene-set enrichment analysis indicated that E2F targets, epithelial–mesenchymal transition, glycolysis, the WNT signaling pathway, and other pathways were highly enriched upon SKA3 upregulation. Gene-set variation analysis of SKA3 and its ten hub genes showed that the significant correlation of cancer-related pathways included the cell cycle, DNA damage, hormone androgen receptor, hormone estrogen receptor, PI3K/Akt, and Ras/MAPK. In addition, we found that MEK inhibitors, ie, trametinib, selumetinib, PD0325901, and RDEA119, may be feasible targeting agents for KIRP patients. Conclusion: SKA3 might contribute to poor prognosis of KIRP through cell cycle, DNA damage, hormone androgen receptor, hormone estrogen receptor, PI3K/Akt, and RAS/MAPK. SKA3 potentially serves as a prognostic biomarker and target for KIRP. Keywords: spindle and kinetochore–associated complex subunit 3, kidney renal papillary cell carcinoma, biomarker, enrichment analysis, targeted therapy