Multi-Omics Identification of UBE2C as a Prognostic Biomarker and Therapeutic Target Linked to Topotecan Sensitivity...

Objectives: Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) necessitate the discovery of novel biomarkers for prognostic and therapeutic advancement. This study aims to evaluate the clinical significance of ubiquitin-conjugating enzyme E2C (UBE2C) and its association with the tumor microenvironment (TME) in CESC. Methods: We meticulously sourced CESC data from renowned repositories such as The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Gene Expression Omnibus (GEO), leveraging cutting-edge techniques including single-cell RNA sequencing (scRNA-seq), spatial transcriptomics, and pharmacogenomics. Through multifaceted data analysis, we endeavored to unravel the intricate role and potential value of UBE2C in CESC tumorigenesis and progression. Results: Analysis of public datasets confirms UBE2C elevation in CESC tumors, correlating with advanced stages, metastasis, and poor disease-free survival (DFS). Dependency screens and functional enrichment highlight UBE2C's critical role in cell viability and DNA replication. Notably, multi-omics and spatial transcriptomics reveal a strong link between UBE2C expression and macrophage infiltration (CD63⁺) in tumor regions. Finally, pharmacogenomic profiling and molecular docking identified Topotecan as a potent therapeutic agent with high UBE2C binding affinity. Conclusion: In conclusion, UBE2C expression is associated with cervical cancer progression and correlates with an immunosuppressive macrophage-enriched microenvironment, making it a promising candidate for further investigation in therapeutic intervention.