Functional genomics identifies five distinct molecular subtypes with clinical relevance and pathways for growth control in epithelial ovarian cancer

EMBO Mol Med. 2013 Jul;5(7):1051-66. doi: 10.1002/emmm.201201823. Epub 2013 May 13.


Epithelial ovarian cancer (EOC) is hallmarked by a high degree of heterogeneity. To address this heterogeneity, a classification scheme was developed based on gene expression patterns of 1538 tumours. Five, biologically distinct subgroups - Epi-A, Epi-B, Mes, Stem-A and Stem-B - exhibited significantly distinct clinicopathological characteristics, deregulated pathways and patient prognoses, and were validated using independent datasets. To identify subtype-specific molecular targets, ovarian cancer cell lines representing these molecular subtypes were screened against a genome-wide shRNA library. Focusing on the poor-prognosis Stem-A subtype, we found that two genes involved in tubulin processing, TUBGCP4 and NAT10, were essential for cell growth, an observation supported by a pathway analysis that also predicted involvement of microtubule-related processes. Furthermore, we observed that Stem-A cell lines were indeed more sensitive to inhibitors of tubulin polymerization, vincristine and vinorelbine, than the other subtypes. This subtyping offers new insights into the development of novel diagnostic and personalized treatment for EOC patients.

Keywords: cell line model for subtype; functional genomic screen; molecular subtype; ovarian cancer; tubulin.

MeSH terms

  • Carcinoma, Ovarian Epithelial
  • Cell Line, Tumor
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Microtubule-Associated Proteins / genetics
  • Microtubules / pathology
  • N-Terminal Acetyltransferase E / genetics
  • N-Terminal Acetyltransferases
  • Neoplasms, Glandular and Epithelial / diagnosis
  • Neoplasms, Glandular and Epithelial / genetics*
  • Neoplasms, Glandular and Epithelial / pathology*
  • Ovarian Neoplasms / diagnosis
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / pathology*
  • Ovary / metabolism
  • Ovary / pathology*
  • Prognosis


  • Microtubule-Associated Proteins
  • TUBGCP4 protein, human
  • N-Terminal Acetyltransferase E
  • N-Terminal Acetyltransferases
  • NAT10 protein, human