ORIGINAL RESEARCH article
Front. Mol. Biosci.
Sec. Molecular Diagnostics and Therapeutics
Volume 12 - 2025 | doi: 10.3389/fmolb.2025.1622496
This article is part of the Research TopicAdvancing Biomarker Discovery, Molecular Mechanisms, and Immunological Insights in Tumor Precision MedicineView all 4 articles
CCDC138 Overexpression Predicts Poor Prognosis and Highlights Ciliopathy-Linked Mechanisms in Uterine Corpus Endometrial Carcinoma
Provisionally accepted
- 1Shaoxing Maternity and Child Health Care Hospital, Shaoxing, China
- 2First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
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Uterine corpus endometrial carcinoma (UCEC) is a common and increasingly prevalent malignancy of the female reproductive system, underscoring the urgent need to elucidate its molecular mechanisms and identify potential biomarkers. Although CCDC138 has been linked to ciliopathies and cancer, its role in UCEC remains unclear. In this study, we integrated transcriptomic and proteomic data from the The Cancer Genome Atlas (TCGA), Clinical Proteomic Tumor Analysis Consortium (CPTAC), and Genotype-Tissue Expression (GTEx) to comprehensively evaluate the expression and functional relevance of CCDC138 in UCEC using bioinformatics approaches, including weighted gene co-expression network analysis (WGCNA), single-sample gene set enrichment analysis (ssGSEA), machine learning, and survival analysis. Our findings revealed that CCDC138 is significantly overexpressed at the mRNA and protein levels in UCEC and is associated with poor overall survival. ssGSEA linked CCDC138 to key oncogenic pathways, such as mTOR, p53/Rb, and MYC/MYCN. Moreover, elevated CCDC138 levels correlated with reduced stromal and immune scores, suggesting a role in modulating immune cell infiltration and tumor microenvironment. Drug sensitivity analysis revealed that high CCDC138 expression is associated with increased responsiveness to chemotherapeutic agents, including 5-fluorouracil and alpelisib. Furthermore, protein-protein interaction analysis identified strong associations with proteins, such as DCTN2 and CEP72. In vitro, CCDC138 knockdown significantly reduced cell proliferation (via CCK8 and EdU assays) and downregulated mTOR, S6K1, and p21 mRNA expression, confirming its role in oncogenic signaling. These findings highlight CCDC138 as a shared target gene in UCEC and ciliopathies, contributing to tumor progression, immune modulation, and therapeutic responsiveness, supporting its potential as a prognostic biomarker and therapeutic target.
Keywords: Uterine corpus endometrial carcinoma, CCDC138, ciliopathy, biomarker, prognosis
Received: 03 May 2025; Accepted: 29 Jul 2025.
Copyright: © 2025 Yang, Wang, Zhang, Li and Fu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Shi Li, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
Han Fu, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
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