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

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.