BACKGROUND Cervical cancer (CC) remains the fourth leading cause of cancer-related deaths in women globally, with poor prognosis for metastatic and recurrent cases. Although genomic alterations have been extensively characterized, global proteogenomic landscape of the disease is largely under explored.METHODS Here, we present the first genome-wide proteogenomic characterization of CC, analyzing 139 tumor-normal tissue pairs using whole-genome sequencing, transcriptomics, proteomics, and phosphoproteomics.RESULTS We identified 4 distinct molecular subtypes with unique clinical outcomes: epithelial-mesenchymal transition (EMT, C1), proliferation (C2), immune response (C3), and epithelial differentiation (C4).
A 4-protein classifier (CDH13, TP53BP1, NNMT, HSPB1) was developed with strong prognostic and predictive value, particularly for immunotherapy response in subtype C3. Phosphoproteomic profiling uncovered subtype-specific kinase activity, identifying actionable therapeutic targets.CONCLUSION Our findings further revealed previously uncharacterized somatic copy number alterations, extrachromosomal DNA landscape, and human-HPV fusion peptides, with implications for genetic heterogeneity and therapeutic targets.
Journal of Clinical Investigation published a clinical update in Research Highlights on 03 Apr 2026.
The item focuses on Proteogenomic characterization of cervical cancer identifies molecular subtypes predictive of clinical outcomes and subtype-specific targets.
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