Downregulation of FXYD2 Is Associated with Poor Prognosis and Increased Regulatory T Cell Infiltration in Clear Cell Renal Cell Carcinoma
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Le résumé fourni par la source
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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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Downregulation of FXYD2 Is Associated with Poor Prognosis and Increased Regulatory T Cell Infiltration in Clear Cell Renal Cell Carcinoma
- Date Crossref
- 19/10/2022
- Éditeur
- Wiley
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Peking University Department of Urology pays non établi dans la noticeUniversité ou école supérieure
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Beijing Chest Hospital pays non établi dans la noticeÉtablissement de santé
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Peking University First Hospital pays non établi dans la noticeÉtablissement de santé
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Shantou University pays non établi dans la noticeUniversité ou école supérieure
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Shantou University Medical College pays non établi dans la noticeUniversité ou école supérieure
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Sun Yat-sen University Department of Hepatobiliary Surgery pays non établi dans la noticeUniversité ou école supérieure
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Sun Yat-sen Memorial Hospital pays non établi dans la noticeÉtablissement de santé
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National Urological Cancer Center pays non établi dans la noticeInstitution
Department of Urology — Peking University, Beijing Chest Hospital et Peking University First Hospital, avec 5 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.