Molecular subtyping of serous ovarian tumors reveals multiple connections to intrinsic breast cancer subtypes

PLoS One. 2014 Sep 16;9(9):e107643. doi: 10.1371/journal.pone.0107643. eCollection 2014.

Abstract

Objective: Transcriptional profiling of epithelial ovarian cancer has revealed molecular subtypes correlating to biological and clinical features. We aimed to determine gene expression differences between malignant, benign and borderline serous ovarian tumors, and investigate similarities with the well-established intrinsic molecular subtypes of breast cancer.

Methods: Global gene expression profiling using Illumina's HT12 Bead Arrays was applied to 59 fresh-frozen serous ovarian malignant, benign and borderline tumors. Nearest centroid classification was performed applying previously published gene profiles for the ovarian and breast cancer subtypes. Correlations to gene expression modules representing key biological breast cancer features were also sought. Validation was performed using an independent, publicly available dataset.

Results: 5,944 genes were significantly differentially expressed between benign and malignant serous ovarian tumors, with cell cycle processes enriched in the malignant subgroup. Borderline tumors were split between the two clusters. Significant correlations between the malignant serous tumors and the highly aggressive ovarian cancer signatures, and the basal-like breast cancer subtype were found. The benign and borderline serous tumors together were significantly correlated to the normal-like breast cancer subtype and the ovarian cancer signature derived from borderline tumors. The borderline tumors in the study dataset, in addition, also correlated significantly to the luminal A breast cancer subtype. These findings remained when analyzed in an independent dataset, supporting links between the molecular subtypes of ovarian cancer and breast cancer beyond those recently acknowledged.

Conclusions: These data link the transcriptional profiles of serous ovarian cancer to the intrinsic molecular subtypes of breast cancer, in line with the shared clinical and molecular features between high-grade serous ovarian cancer and basal-like breast cancer, and suggest that biomarkers and targeted therapies may overlap between these tumor subsets. The link between benign and borderline ovarian cancer and luminal breast cancer may indicate endocrine responsiveness in a subset of ovarian cancers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Breast Neoplasms / diagnosis*
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / mortality
  • Cluster Analysis
  • Cystadenoma, Serous / diagnosis*
  • Cystadenoma, Serous / genetics*
  • Cystadenoma, Serous / mortality
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Genes, ras
  • Humans
  • Middle Aged
  • Mutation
  • Neoplasm Grading
  • Neoplasm Staging
  • Ovarian Neoplasms / diagnosis*
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / mortality
  • Proto-Oncogene Proteins B-raf / genetics
  • Reproducibility of Results

Substances

  • Proto-Oncogene Proteins B-raf

Associated data

  • GEO/GSE57477

Grants and funding

Financial support was granted from a governmental funding of clinical research within the National Health Services (JMJ), the Swedish Cancer Society (MN, IH), the Swedish Research Council (MN, IH) and an unrestricted educational grant from the Swedish Society of Gynecologic Oncology sponsored by Roche (JMJ). Funding has neither influenced study design, data collection nor analysis or manuscript writing.