From Biomarker to Drug Target: Integrating ceRNA Networks and Pharmacogenomics to Reposition C5orf34 in Uterine Corpus Endometrial Cancer Therapy

INTRODUCTION: This study aimed to systematically investigate the expression, prognostic value, biological roles, and therapeutic relevance of C5orf34 in uterine corpus endometrial carcinoma (UCEC). METHODS: Using TCGA-UCEC data (554 tumor vs. 35 normal samples), we performed differential expression analysis, survival modeling, gene-set enrichment (GSEA), immune-infiltration profiling (TIMER/CIBERSORT), drug-sensitivity prediction (RNAactDrug), and ceRNA network construction. C5orf34 expression was validated by qRT-PCR in UCEC cell lines (Ishikawa, KLE) and by immunohistochemistry via the Human Protein Atlas. RESULTS: The expression of C5orf34 was significantly higher in UCEC tissues than in normal endometrial tissues (p < 0.001). Increased C5orf34 expression was linked to advanced clinical stage (p < 0.001), older age (p < 0.001), higher weight (p = 0.011), and specific histological types (p < 0.001). Elevated C5orf34 expression was identified as an independent risk factor for poorer overall survival (OS, HR: 2.184; p = 0.015), progression-free survival (PFS, HR: 1.68; p = 0.004), and disease-specific survival (DSS, HR: 3.28; p < 0.001). GSEA analysis indicated that C5orf34 was associated with pathways like cell cycle regulation, cytokine-cytokine receptor interaction, DNA replication, and immune-related processes. The expression of C5orf34 was negatively correlated with immune cell infiltration, such as NK CD56bright cells, and immune scores, implying an immunosuppressive tumor microenvironment. Furthermore, C5orf34 expression was associated with resistance to several drugs, including AT-7519, Navitoclax, Tivozanib, Ruxolitinib, and Erlotinib. A ceRNA network involving LNC01224/miR-455-5p/C5orf34 was constructed, providing insights into the regulatory mechanisms of C5orf34 in UCEC. DISCUSSION: C5orf34 emerges as a novel oncogenic driver and immunomodulator in UCEC, linking tumor proliferation, immune evasion, and chemoresistance. Limitations include reliance on public databases and the need for functional mechanistic studies. CONCLUSION: This research identifies C5orf34 as a potential prognostic indicator and therapeutic target for UCEC. The results underscore the significance of C5orf34 in tumor progression, immune regulation, and drug resistance. Future studies should concentrate on clarifying the molecular mechanisms of C5orf34 and verifying its clinical application in larger cohorts.