Department of Urology, Peking University First Hospital, Beijing, China.
Hereditary Kidney Cancer Research Center, Peking University First Hospital, Beijing, China.
J Immunol Res. 2022 Oct 19;2022:4946197. doi: 10.1155/2022/4946197. eCollection 2022.
FXYD2, a gene coding for the 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. . 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.
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--SMAD2/3, Notch, and PI3K-Akt-mTOR signaling pathways may be potential signaling pathways of FXYD2 in ccRCC.
Downregulation of FXYD2 is associated with ccRCC tumorigenesis, poor prognosis, and increased Treg infiltration in ccRCC, which may be related to TGF--SMAD2/3, Notch, and PI3K-Akt-mTOR signaling pathways. This will probably provide a novel prognostic marker and potential therapeutic target for ccRCC.
FXYD2 是编码 Na/K-ATP 酶亚基的基因，最近被证明参与了癌症的发生。然而，FXYD2 在透明细胞肾细胞癌（ccRCC）中的具体作用仍不清楚。本研究旨在探讨 FXYD2 在 ccRCC 中的表达、生物学功能及潜在的免疫相关机制。利用 TCGA-KIRC、ICGC、GEO、Oncomine、ArrayExpress、TIMER、HPA 数据集和我们的临床样本，确定和验证 FXYD2 在 ccRCC 中的表达水平、预后作用和潜在的免疫相关机制。通过细胞功能测定，研究 FXYD2 在体外的生物学作用。
与正常组织相比，ccRCC 组织中 FXYD2 的表达下调，这一结果通过我们的 RT-PCR、WB 和 IHC 分析得到了验证。Kaplan-Meier 生存分析和 Cox 回归分析表明，下调的 FXYD2 可独立预测 ccRCC 患者的不良预后。通过 ESTIMATE 算法、ssGSEA 算法、CIBERSORT 算法、TIMER 数据库和我们的实验室实验发现，FXYD2 与 ccRCC 的免疫图谱相关，尤其是调节性 T 细胞（Treg）。功能获得实验表明，FXYD2 可抑制细胞在体外的增殖、迁移和侵袭。功能富集分析表明，TGF-β-SMAD2/3、Notch 和 PI3K-Akt-mTOR 信号通路可能是 FXYD2 在 ccRCC 中的潜在信号通路。
FXYD2 的下调与 ccRCC 的肿瘤发生、不良预后和 ccRCC 中 Treg 浸润增加有关，这可能与 TGF-β-SMAD2/3、Notch 和 PI3K-Akt-mTOR 信号通路有关。这可能为 ccRCC 提供一个新的预后标志物和潜在的治疗靶点。
