Downregulation of FXYD2 Is Associated with Poor Prognosis and Increased Regulatory T Cell Infiltration in Clear Cell Renal Cell Carcinoma
Background. FXYD2, a gene coding for the γ subunit of Na+/K+-ATPase, was demonstrated to involve in carcinogenesis recently. However, the specific role of FXYD2 in clear cell renal cell carcinoma (ccRCC) remains unknown. The current study was conducted to investigate the expression, biological funct...
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| Format: | Article |
| Language: | English |
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Wiley
2022-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2022/4946197 |
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| author | Zedan Zhang Yanlin Tang Lei Li Wuping Yang Yawei Xu Jingcheng Zhou Kaifang Ma Kenan Zhang Hongkai Zhuang Yanqing Gong Kan Gong |
| author_facet | Zedan Zhang Yanlin Tang Lei Li Wuping Yang Yawei Xu Jingcheng Zhou Kaifang Ma Kenan Zhang Hongkai Zhuang Yanqing Gong Kan Gong |
| author_sort | Zedan Zhang |
| collection | DOAJ |
| description | Background. FXYD2, a gene coding for the γ subunit of Na+/K+-ATPase, was demonstrated to involve in carcinogenesis recently. However, the specific role of FXYD2 in clear cell renal cell carcinoma (ccRCC) remains unknown. The current study was conducted to investigate the expression, biological function, and potentially immune-related mechanisms of FXYD2 in ccRCC. Materials and methods. The data from TCGA-KIRC, ICGC, GEO, Oncomine, ArrayExpress, TIMER, HPA datasets, and our clinical samples were used to determine and validate the expression level, prognostic roles, and potentially immune-related mechanisms in ccRCC. Cell function assays were performed to investigate the biological role of FXYD2 in vitro. Results. FXYD2 was identified to be downregulated in ccRCC tissue compared to normal tissue, which was confirmed by our RT-PCR, WB, and IHC analyses. Kaplan-Meier survival analysis and Cox regression analysis suggested that downregulated FXYD2 could independently predict poor survival of ccRCC patients. Through the ESTIMATE algorithm, ssGSEA algorithm, CIBERSORT algorithm, TIMER database, and our laboratory experiment, FXYD2 was found to correlate with the immune landscape, especially regulatory T cells (Treg), in ccRCC. Gain-of-function experiment revealed that FXYD2 could restrain cell proliferation, migration, and invasion in vitro. Functional enrichment analysis illustrated that TGF-β-SMAD2/3, Notch, and PI3K-Akt-mTOR signaling pathways may be potential signaling pathways of FXYD2 in ccRCC. Conclusions. Downregulation of FXYD2 is associated with ccRCC tumorigenesis, poor prognosis, and increased Treg infiltration in ccRCC, which may be related to TGF-β-SMAD2/3, Notch, and PI3K-Akt-mTOR signaling pathways. This will probably provide a novel prognostic marker and potential therapeutic target for ccRCC. |
| format | Article |
| id | doaj-art-0b47f4c934f847dc87c6e8d842ecf064 |
| institution | Kabale University |
| issn | 2314-7156 |
| language | English |
| publishDate | 2022-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-0b47f4c934f847dc87c6e8d842ecf0642025-02-03T06:13:02ZengWileyJournal of Immunology Research2314-71562022-01-01202210.1155/2022/4946197Downregulation of FXYD2 Is Associated with Poor Prognosis and Increased Regulatory T Cell Infiltration in Clear Cell Renal Cell CarcinomaZedan Zhang0Yanlin Tang1Lei Li2Wuping Yang3Yawei Xu4Jingcheng Zhou5Kaifang Ma6Kenan Zhang7Hongkai Zhuang8Yanqing Gong9Kan Gong10Department of UrologyShantou University Medical CollegeDepartment of UrologyDepartment of UrologyDepartment of UrologyDepartment of UrologyDepartment of UrologyDepartment of UrologyDepartment of Hepatobiliary SurgeryDepartment of UrologyDepartment of UrologyBackground. FXYD2, a gene coding for the γ subunit of Na+/K+-ATPase, was demonstrated to involve in carcinogenesis recently. However, the specific role of FXYD2 in clear cell renal cell carcinoma (ccRCC) remains unknown. The current study was conducted to investigate the expression, biological function, and potentially immune-related mechanisms of FXYD2 in ccRCC. Materials and methods. The data from TCGA-KIRC, ICGC, GEO, Oncomine, ArrayExpress, TIMER, HPA datasets, and our clinical samples were used to determine and validate the expression level, prognostic roles, and potentially immune-related mechanisms in ccRCC. Cell function assays were performed to investigate the biological role of FXYD2 in vitro. Results. FXYD2 was identified to be downregulated in ccRCC tissue compared to normal tissue, which was confirmed by our RT-PCR, WB, and IHC analyses. Kaplan-Meier survival analysis and Cox regression analysis suggested that downregulated FXYD2 could independently predict poor survival of ccRCC patients. Through the ESTIMATE algorithm, ssGSEA algorithm, CIBERSORT algorithm, TIMER database, and our laboratory experiment, FXYD2 was found to correlate with the immune landscape, especially regulatory T cells (Treg), in ccRCC. Gain-of-function experiment revealed that FXYD2 could restrain cell proliferation, migration, and invasion in vitro. Functional enrichment analysis illustrated that TGF-β-SMAD2/3, Notch, and PI3K-Akt-mTOR signaling pathways may be potential signaling pathways of FXYD2 in ccRCC. Conclusions. Downregulation of FXYD2 is associated with ccRCC tumorigenesis, poor prognosis, and increased Treg infiltration in ccRCC, which may be related to TGF-β-SMAD2/3, Notch, and PI3K-Akt-mTOR signaling pathways. This will probably provide a novel prognostic marker and potential therapeutic target for ccRCC.http://dx.doi.org/10.1155/2022/4946197 |
| spellingShingle | Zedan Zhang Yanlin Tang Lei Li Wuping Yang Yawei Xu Jingcheng Zhou Kaifang Ma Kenan Zhang Hongkai Zhuang Yanqing Gong Kan Gong Downregulation of FXYD2 Is Associated with Poor Prognosis and Increased Regulatory T Cell Infiltration in Clear Cell Renal Cell Carcinoma Journal of Immunology Research |
| title | Downregulation of FXYD2 Is Associated with Poor Prognosis and Increased Regulatory T Cell Infiltration in Clear Cell Renal Cell Carcinoma |
| title_full | Downregulation of FXYD2 Is Associated with Poor Prognosis and Increased Regulatory T Cell Infiltration in Clear Cell Renal Cell Carcinoma |
| title_fullStr | Downregulation of FXYD2 Is Associated with Poor Prognosis and Increased Regulatory T Cell Infiltration in Clear Cell Renal Cell Carcinoma |
| title_full_unstemmed | Downregulation of FXYD2 Is Associated with Poor Prognosis and Increased Regulatory T Cell Infiltration in Clear Cell Renal Cell Carcinoma |
| title_short | Downregulation of FXYD2 Is Associated with Poor Prognosis and Increased Regulatory T Cell Infiltration in Clear Cell Renal Cell Carcinoma |
| title_sort | downregulation of fxyd2 is associated with poor prognosis and increased regulatory t cell infiltration in clear cell renal cell carcinoma |
| url | http://dx.doi.org/10.1155/2022/4946197 |
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