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多维度综合分析 TMEM25 在低表达状态下的肾透明细胞癌潜在功能。

Multidimensional comprehensive and integrated analysis of the potential function of TMEM25 in renal clear cell carcinoma with low expression status.

机构信息

Department of Urology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China.

Department of Surgery, Fuzhou First People’s Hospital, Fuzhou 344000, Jiangxi Province, China.

出版信息

Aging (Albany NY). 2024 Jan 5;16(1):367-388. doi: 10.18632/aging.205372.

DOI:10.18632/aging.205372
PMID:38189809
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10817401/
Abstract

BACKGROUND

Transmembrane 25(TMEM25) stands out as a potential prognostic biomarker and therapeutic target in the realm of cancer, yet its precise mechanism of action within clear cell renal cell carcinoma (ccRCC) remains unclear.

MATERIALS AND METHODS

Gene expression data and clinically relevant information extracted from The Cancer Genome Atlas (TCGA) and Gene expression omnibus (GEO) databases unveil the expression patterns of TMEM25 within renal clear cell carcinoma, which reveals its prognostic and diagnostic significance. The protein expression data is available via the Human Protein Atlas (HPA) database. Further, qPCR experiments conducted on cells and tissues provide strong evidence of the gene's expression status. Additionally, they explore the correlations between TMEM25 expression and DNA methylation, gene mutations, immune cell infiltration, and drug sensitivity within this specific tumor context.

RESULTS

At both the RNA and protein levels, TMEM25 displays a noteworthy downregulation in expression, which is consistently linked to an unfavorable prognosis. Receiver Operating Characteristic (ROC) curve analysis, univariate and multivariate Cox regression analyses confirmed the ability of TMEM25 to diagnose and determine prognosis in ccRCC. Its expression related closely with various immune cell types, immune checkpoints, immune inhibitors, and MHC molecules. Within ccRCC tissues, TMEM25 DNA methylation levels are observed to be elevated, and this upregulation is observed across various conditions. TMEM25 mutations also have an impact on the prognosis of ccRCC patients and the results of drug sensitivity analyses are useful for clinical decision-making.

CONCLUSIONS

TMEM25 in ccRCC could potentially function as a tumor suppressor gene, holding substantial promise as a novel biomarker for diagnosing, treating, and prognosticating ccRCC patients.

摘要

背景

跨膜蛋白 25(TMEM25)作为癌症领域的一个有潜力的预后生物标志物和治疗靶点而备受关注,但它在透明细胞肾细胞癌(ccRCC)中的确切作用机制尚不清楚。

材料和方法

从癌症基因组图谱(TCGA)和基因表达综合数据库(GEO)中提取基因表达数据和临床相关信息,揭示了 TMEM25 在肾透明细胞癌中的表达模式,揭示了其预后和诊断意义。HPA 数据库提供了 TMEM25 的蛋白表达数据。此外,在细胞和组织上进行的 qPCR 实验提供了强有力的证据证明该基因的表达状态。此外,它们还探讨了在特定肿瘤环境中 TMEM25 表达与 DNA 甲基化、基因突变、免疫细胞浸润和药物敏感性之间的相关性。

结果

在 RNA 和蛋白水平上,TMEM25 的表达均显著下调,且与预后不良密切相关。ROC 曲线分析、单变量和多变量 Cox 回归分析证实了 TMEM25 对 ccRCC 的诊断和预后判断能力。它的表达与各种免疫细胞类型、免疫检查点、免疫抑制剂和 MHC 分子密切相关。在 ccRCC 组织中,观察到 TMEM25 的 DNA 甲基化水平升高,且在各种情况下均可见上调。TMEM25 突变也会影响 ccRCC 患者的预后,且药物敏感性分析的结果有助于临床决策。

结论

ccRCC 中的 TMEM25 可能作为肿瘤抑制基因发挥作用,作为诊断、治疗和预测 ccRCC 患者的新型生物标志物具有很大的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe81/10817401/f2cde22d046d/aging-16-205372-g008.jpg
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Downregulation of lncRNA APCDD1L-AS1 due to DNA hypermethylation and loss of VHL protein expression promotes the progression of clear cell renal cell carcinoma.由于 DNA 过度甲基化和 VHL 蛋白表达缺失导致 lncRNA APCDD1L-AS1 下调,促进了透明细胞肾细胞癌的进展。
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Cancer statistics, 2022.癌症统计数据,2022 年。
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