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The sub-molecular characterization identification for cervical cancer.

XinKai Mo1, Na Wang2, Zanjing He2

  • 1Department of Clinical Laboratory, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan 250117, Shandong, PR China.

Heliyon
|July 24, 2023
PubMed
Summary

This study identified two molecular subtypes of cervical cancer (CESC) with distinct prognoses. A novel classifier accurately distinguishes subtypes and highlights GALNT2 as a potential therapeutic target for CESC.

Keywords:
Cervical cancerClassifierGALNT2Non-negative matrix factorization

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Area of Science:

  • Oncology
  • Molecular Biology
  • Genomics

Background:

  • Cervical cancer (CESC) treatment efficacy is limited by molecular heterogeneity.
  • Sub-molecular characterization is crucial for personalized CESC treatment strategies.

Purpose of the Study:

  • To classify CESC patients into molecular subtypes.
  • To develop a classifier for sub-molecular characterization.
  • To explore the biological and prognostic implications of these subtypes.

Main Methods:

  • Utilized NMF, random forest, and Cox analysis on TCGA and GEO datasets (741 CESC patients).
  • Validated classifier gene significance using molecular and cellular assays (qPCR, Western blot, proliferation, migration assays).

Main Results:

  • Identified two CESC subtypes; one associated with poorer prognosis, altered signaling pathways (ECM-receptor, PI3K-Akt, MAPK), immune cell infiltration (M0 Macrophage, resting Mast cells), and low HLA gene expression.
  • Developed a highly accurate classifier (AUC > 0.96) outperforming existing CESC signatures.
  • Demonstrated GALNT2's role in proliferation, migration, and epithelial-mesenchymal transition, suggesting it as a therapeutic target.

Conclusions:

  • The constructed classifier enhances understanding of CESC subtypes and offers a new therapeutic strategy.
  • GALNT2 emerges as a potential direct therapeutic target for cervical cancer.