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 Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China*These authors contributed equally to this wor...
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Dove Medical Press
2021
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oai:doaj.org-article:1f15af594f9d4a6ab6fc9c961afffb162021-11-23T18:43:01ZSKA3 Serves as a Biomarker for Poor Prognosis in Kidney Renal Papillary Cell Carcinoma1178-7074https://doaj.org/article/1f15af594f9d4a6ab6fc9c961afffb162021-11-01T00:00:00Zhttps://www.dovepress.com/ska3-serves-as-a-biomarker-for-poor-prognosis-in-kidney-renal-papillar-peer-reviewed-fulltext-article-IJGMhttps://doaj.org/toc/1178-7074Dechao Feng,* Facai Zhang,* Ling Liu,* Qiao Xiong, Hang Xu, Wuran Wei, Zhenghua Liu, Lu Yang Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhenghua Liu; Lu YangDepartment of Urology, Institute of Urology, West China Hospital, Sichuan University, 37 Guoxue Xiang, Chengdu, 610041, Sichuan, People’s Republic of ChinaTel +86 28-8542-2444Fax +86 28-85422451Email zhliu@scu.edu.cn; wycleflue@163.comBackground: 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 therapyFeng DZhang FLiu LXiong QXu HWei WLiu ZYang LDove Medical Pressarticlespindle and kinetochore associated complex subunit 3kidney renal papillary cell carcinomabiomarkerenrichment analysistargeted therapyMedicine (General)R5-920ENInternational Journal of General Medicine, Vol Volume 14, Pp 8591-8602 (2021) |
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spindle and kinetochore associated complex subunit 3 kidney renal papillary cell carcinoma biomarker enrichment analysis targeted therapy Medicine (General) R5-920 |
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spindle and kinetochore associated complex subunit 3 kidney renal papillary cell carcinoma biomarker enrichment analysis targeted therapy Medicine (General) R5-920 Feng D Zhang F Liu L Xiong Q Xu H Wei W Liu Z Yang L SKA3 Serves as a Biomarker for Poor Prognosis in Kidney Renal Papillary Cell Carcinoma |
| description |
Dechao Feng,* Facai Zhang,* Ling Liu,* Qiao Xiong, Hang Xu, Wuran Wei, Zhenghua Liu, Lu Yang Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhenghua Liu; Lu YangDepartment of Urology, Institute of Urology, West China Hospital, Sichuan University, 37 Guoxue Xiang, Chengdu, 610041, Sichuan, People’s Republic of ChinaTel +86 28-8542-2444Fax +86 28-85422451Email zhliu@scu.edu.cn; wycleflue@163.comBackground: 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 |
| format |
article |
| author |
Feng D Zhang F Liu L Xiong Q Xu H Wei W Liu Z Yang L |
| author_facet |
Feng D Zhang F Liu L Xiong Q Xu H Wei W Liu Z Yang L |
| author_sort |
Feng D |
| title |
SKA3 Serves as a Biomarker for Poor Prognosis in Kidney Renal Papillary Cell Carcinoma |
| title_short |
SKA3 Serves as a Biomarker for Poor Prognosis in Kidney Renal Papillary Cell Carcinoma |
| title_full |
SKA3 Serves as a Biomarker for Poor Prognosis in Kidney Renal Papillary Cell Carcinoma |
| title_fullStr |
SKA3 Serves as a Biomarker for Poor Prognosis in Kidney Renal Papillary Cell Carcinoma |
| title_full_unstemmed |
SKA3 Serves as a Biomarker for Poor Prognosis in Kidney Renal Papillary Cell Carcinoma |
| title_sort |
ska3 serves as a biomarker for poor prognosis in kidney renal papillary cell carcinoma |
| publisher |
Dove Medical Press |
| publishDate |
2021 |
| url |
https://doaj.org/article/1f15af594f9d4a6ab6fc9c961afffb16 |
| work_keys_str_mv |
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