Publication Date

11-22-2024

Journal

Nature Communications

DOI

10.1038/s41467-024-53830-0

PMID

39578447

PMCID

PMC11584810

PubMedCentral® Posted Date

11-22-2024

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Humans, Female, Uterine Cervical Neoplasms, Proteogenomics, E1A-Associated p300 Protein, Protein Kinase C beta, Middle Aged, Biomarkers, Tumor, Proto-Oncogene Proteins c-fos, Acetylation, Papillomavirus Infections, Adult, Prognosis, Gene Expression Regulation, Neoplastic, Cell Line, Tumor, Cell Proliferation, Protein Processing, Post-Translational, Papillomaviridae, Cervical cancer, Cancer genomics, Tumour biomarkers, Proteomics

Abstract

Although the incidence of cervical cancer (CC) has been reduced in high-income countries due to human papillomavirus (HPV) vaccination and screening strategies, it remains a significant public health issue that poses a threat to women's health in low-income countries. Here, we perform a comprehensive proteogenomic profiling of CC tumors obtained from 139 Chinese women. Integrated proteogenomic analysis links genetic aberrations to downstream pathogenesis-related pathways and reveals the landscape of HPV-associated multi-omic changes. EP300 is found to enhance the acetylation of FOSL2-K222, consequently accelerating the malignant proliferation of CC cells. Proteomic stratification identifies three patient subgroups with distinct features in prognosis, genetic alterations, immune infiltration, and post-translational modification regulations. PRKCB is further identified as a potential radioresponse-related biomarker of CC patients. This study provides a valuable public resource for researchers and clinicians to delve into the molecular basis of CC, to identify potential treatments and to ultimately advance clinical practice.

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