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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 f...

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Autores principales: Zhang, Zedan, Tang, Yanlin, Li, Lei, Yang, Wuping, Xu, Yawei, Zhou, Jingcheng, Ma, Kaifang, Zhang, Kenan, Zhuang, Hongkai, Gong, Yanqing, Gong, Kan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9606837/
https://www.ncbi.nlm.nih.gov/pubmed/36313180
http://dx.doi.org/10.1155/2022/4946197
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author Zhang, Zedan
Tang, Yanlin
Li, Lei
Yang, Wuping
Xu, Yawei
Zhou, Jingcheng
Ma, Kaifang
Zhang, Kenan
Zhuang, Hongkai
Gong, Yanqing
Gong, Kan
author_facet Zhang, Zedan
Tang, Yanlin
Li, Lei
Yang, Wuping
Xu, Yawei
Zhou, Jingcheng
Ma, Kaifang
Zhang, Kenan
Zhuang, Hongkai
Gong, Yanqing
Gong, Kan
author_sort Zhang, Zedan
collection PubMed
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.
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spelling pubmed-96068372022-10-28 Downregulation of FXYD2 Is Associated with Poor Prognosis and Increased Regulatory T Cell Infiltration in Clear Cell Renal Cell Carcinoma Zhang, Zedan Tang, Yanlin Li, Lei Yang, Wuping Xu, Yawei Zhou, Jingcheng Ma, Kaifang Zhang, Kenan Zhuang, Hongkai Gong, Yanqing Gong, Kan J Immunol Res Research Article 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. Hindawi 2022-10-19 /pmc/articles/PMC9606837/ /pubmed/36313180 http://dx.doi.org/10.1155/2022/4946197 Text en Copyright © 2022 Zedan Zhang et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Zhang, Zedan
Tang, Yanlin
Li, Lei
Yang, Wuping
Xu, Yawei
Zhou, Jingcheng
Ma, Kaifang
Zhang, Kenan
Zhuang, Hongkai
Gong, Yanqing
Gong, Kan
Downregulation of FXYD2 Is Associated with Poor Prognosis and Increased Regulatory T Cell Infiltration in Clear Cell Renal Cell Carcinoma
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
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9606837/
https://www.ncbi.nlm.nih.gov/pubmed/36313180
http://dx.doi.org/10.1155/2022/4946197
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