Integrative prognostic subtype discovery in high-grade serous ovarian cancer

J Cell Biochem. 2019 Nov;120(11):18659-18666. doi: 10.1002/jcb.29049. Epub 2019 Jul 26.

Abstract

Objective: We sought to identify novel molecular subtypes of high-grade serous ovarian cancer (HGSC) by the integration of gene expression and proteomics data and to find the underlying biological characteristics of ovarian cancer to improve the clinical outcome.

Methods: The iCluster method was utilized to analysis 131 common HGSC samples between TCGA and Clinical Proteomic Tumor Analysis Consortium databases. Kaplan-Meier survival curves were used to estimate the overall survival of patients, and the differences in survival curves were assessed using the log-rank test.

Results: Two novel ovarian cancer subtypes with different overall survival (P = .00114) and different platinum status (P = .0061) were identified. Eighteen messenger RNAs and 38 proteins were selected as differential molecules between subtypes. Pathway analysis demonstrated arrhythmogenic right ventricular cardiomyopathy pathway played a critical role in the discrimination of these two subtypes and desmosomal cadherin DSG2, DSP, JUP, and PKP2 in this pathway were overexpression in subtype I compared with subtype II.

Conclusion: Our study extended the underlying prognosis-related biological characteristics of high-grade serous ovarian cancer. Enrichment of desmosomal cadherin increased the risk for HGSC prognosis among platinum-sensitive patients, the results guided the revision of the treatment options for platinum-sensitive ovarian cancer patients to improve outcomes.

Keywords: high-grade serous ovarian cancer; integration; platinum sensitive; prognosis; subtypes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Cystadenocarcinoma, Serous / classification
  • Cystadenocarcinoma, Serous / genetics*
  • Cystadenocarcinoma, Serous / metabolism
  • Desmosomal Cadherins / genetics
  • Desmosomal Cadherins / metabolism
  • Female
  • Gene Expression Profiling / methods*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Kaplan-Meier Estimate
  • Middle Aged
  • Neoplasm Grading
  • Ovarian Neoplasms / classification
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / metabolism
  • Ovary / drug effects
  • Ovary / metabolism
  • Ovary / pathology
  • Platinum / therapeutic use
  • Prognosis
  • Proteomics / methods*

Substances

  • Biomarkers, Tumor
  • Desmosomal Cadherins
  • Platinum