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

doi:10.2147/IJGM.S336799

SKA3 Serves as a Biomarker for Poor Prognosis in Kidney Renal Papillary Cell Carcinoma

Int J Gen Med. 2021 Nov 23:14:8591-8602. doi: 10.2147/IJGM.S336799. eCollection 2021.

Authors

Dechao Feng^#¹, Facai Zhang^#¹, Ling Liu^#¹, Qiao Xiong¹, Hang Xu¹, Wuran Wei¹, Zhenghua Liu¹, Lu Yang¹

Affiliation

¹ Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, 610041, People's Republic of China.

^# Contributed equally.

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: biomarker; enrichment analysis; kidney renal papillary cell carcinoma; spindle and kinetochore–associated complex subunit 3; targeted therapy.

Grants and funding

This program was supported by the National Natural Science Foundation of China (grant nos. 81974099, 82170785, 81974098, and 82170784), programs from Science and Technology Department of Sichuan Province (grant no. 21GJHZ0246), Young Investigator Award of Sichuan University 2017 (grant no. 2017SCU04A17), Technology Innovation Research and Development Project of Chengdu Science and Technology Bureau (2019-YF05-00296-SN), and the Sichuan University--Panzhihua science and technology cooperation special fund (2020CDPZH-4). The funders had no role in study design, data collection or analysis, preparation of the manuscript, or the decision to publish.