Research Paper Volume 16, Issue 1 pp 367—388

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

Ping Xi1, *, , Zhicheng Zhang2, *, , Yifu Liu1, *, , Yechen Nie1, , Binbin Gong1, , Ji Liu1, , Hao Huang1, , Ziwen Liu1, , Ting Sun1, , Wenjie Xie1, ,

  • 1 Department of Urology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China
  • 2 Department of Surgery, Fuzhou First People’s Hospital, Fuzhou 344000, Jiangxi Province, China
* Equal contribution

Received: September 4, 2023       Accepted: November 21, 2023       Published: January 5, 2024      

https://doi.org/10.18632/aging.205372
How to Cite

Copyright: © 2024 Xi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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.

Abbreviations

ANKRD13B: Ankyrin repeat domain-containing protein 13B; AUC: Area Under the Curve; BAP1: BRCA1-associated protein-1; BP: Biological processes; BRCA: Breast invasive carcinoma; CC: Cell components; ccRCC: Clear cell renal carcinoma; CESC: Cervical squamous cell carcinoma and endocervical adenocarcinoma; COAD: Colon adenocarcinoma; DCA: Decision Curve Analysis; DSS: Disease-Specific Survival; EYS: Eyes shut homolog; FAM19A4: Family with sequence similarity 19 (chemokine (C-C motif)-like), member A4; GBM: Glioblastoma multiform; GEO: Gene expression omnibus; GO: Gene Ontology; GSEA: Gene Set Enrichment Analysis; HPA: The Human Protein; HR: Hazard Ratio; KEGG: Kyoto Encyclopedia of Genes and Genomes; KICH: Kidney chromophobe; KIRC: Kidney renal clear cell; KIRP: Kidney renal papillary cell carcinoma; LICH: Liver hepatocellular carcino; LPPR3: The lipid phosphate phosphatase-related protein3; LUAD: Lung adenocarcinoma; MF: Molecular function; MHC: The major histocompatibility complex; OS: Overall Survival; PCDH20: Protocadherin 20; PFI: Progression-Free Interval; PIP5KL1: Phosphatidylinositol 4-phosphate 5-kinase like protein-1; PNKD: Paroxysmal non-kinesigenic dystonia; qPCR: Quantitative real-time polymerase chain reaction; RCC: Renal cell carcinoma; READ: Rectum adenocarcinoma; ROC: Receiver Operating Characteristic Curve; SETD2: SET domain containing 2; STAD: Stomach adenocarcin; TCGA: The Cancer Genome Atlas; TMEM: Transmembrane; TMEM116: Transmembrane 116; TMEM165: Transmembrane 165; TMEM207: Transmembrane 207; TMEM25: Transmembrane 25; TMEM39A: Transmembrane 39A; TMEM45B: Transmembrane 45B; TMEM91: Transmembrane 91; TMEM97: Transmembrane 97; UCEC: Uterine corpus endometrial carcin; UNC80: Unc-80 homolog; XIRP2: Xin actin binding repeat containing 2.