A proteogenomic analysis of cervical cancer reveals therapeutic and biological insights

Nat Commun. 2024 Nov 22;15(1):10114. doi: 10.1038/s41467-024-53830-0.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Adult
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Cell Line, Tumor
  • Cell Proliferation
  • E1A-Associated p300 Protein* / genetics
  • E1A-Associated p300 Protein* / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Middle Aged
  • Papillomaviridae / genetics
  • Papillomavirus Infections / genetics
  • Papillomavirus Infections / virology
  • Prognosis
  • Protein Kinase C beta / genetics
  • Protein Kinase C beta / metabolism
  • Protein Processing, Post-Translational
  • Proteogenomics* / methods
  • Proto-Oncogene Proteins c-fos / genetics
  • Proto-Oncogene Proteins c-fos / metabolism
  • Uterine Cervical Neoplasms* / genetics
  • Uterine Cervical Neoplasms* / metabolism
  • Uterine Cervical Neoplasms* / pathology
  • Uterine Cervical Neoplasms* / virology

Substances

  • E1A-Associated p300 Protein
  • EP300 protein, human
  • Protein Kinase C beta
  • Biomarkers, Tumor
  • Proto-Oncogene Proteins c-fos