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

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

Ethics

Data are from the literature and public databases. As such, approval from the West China Hospital of Sichuan University Biomedical Research Ethics Committee was not required. The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Acknowledgments

The results shown here are in whole or part based upon data generated by TCGA (https://www.cancer.gov/tcga). Dechao Feng, Facai Zhang, and Ling Liu contributed equally to this work, and should be considered co–first authors. Zhenghua Liu and Lu Yang are co–corresponding authors.

Disclosure

The authors have no conflicts of interest related to this work to declare.

Additional information

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.