Profiling of Discrete Gynecological Cancers Reveals Novel Transcriptional Modules and Common Features Shared by Other Cancer Types and Embryonic Stem Cells

PLoS One. 2015 Nov 11;10(11):e0142229. doi: 10.1371/journal.pone.0142229. eCollection 2015.

Abstract

Studies on individual types of gynecological cancers (GCs), utilizing novel expression technologies, have revealed specific pathogenetic patterns and gene markers for cervical (CC), endometrial (EC) and vulvar cancer (VC). Although the clinical phenotypes of the three types of gynecological cancers are discrete, the fact they originate from a common embryological origin, has led to the hypothesis that they might share common features reflecting regression to early embryogenesis. To address this question, we performed a comprehensive comparative analysis of their profiles. Our data identified both common features (pathways and networks) and novel distinct modules controlling the same deregulated biological processes in all three types. Specifically, four novel transcriptional modules were discovered regulating cell cycle and apoptosis. Integration and comparison of our data with other databases, led to the identification of common features among cancer types, embryonic stem (ES) cells and the newly discovered cell population of squamocolumnar (SC) junction of the cervix, considered to host the early cancer events. Conclusively, these data lead us to propose the presence of common features among gynecological cancers, other types of cancers, ES cells and the pre-malignant SC junction cells, where the novel E2F/NFY and MAX/CEBP modules play an important role for the pathogenesis of gynecological carcinomas.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • Down-Regulation
  • Embryonic Stem Cells / cytology
  • Embryonic Stem Cells / metabolism*
  • Endometrial Neoplasms / genetics
  • Endometrial Neoplasms / pathology
  • Female
  • Gene Expression Profiling
  • Genital Neoplasms, Female / genetics*
  • Genital Neoplasms, Female / pathology
  • Humans
  • Oligonucleotide Array Sequence Analysis
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Up-Regulation
  • Uterine Cervical Neoplasms / genetics
  • Uterine Cervical Neoplasms / pathology
  • Vulvar Neoplasms / genetics
  • Vulvar Neoplasms / pathology

Substances

  • Transcription Factors

Associated data

  • GEO/GSE63678

Grants and funding

This work was supported by the Oncology Program of the Central Council of Health of the Ministry of Health, Grant No. 70-3-9209 (www.moh.gov.gr); by the Empirikion Foundation, Grant No. 70-3-7345 to NPA (www.empirikion.gr); and by the European Union’s European Social Fund (ESF) and Greek National Funds through the Program THALIS, under the Operational Program Education and Lifelong Learning of the National Strategic Reference Framework (NSRF), Grant No. 70-3-11830 to KIP (http://excellence.minedu.gov.gr/thales/en/).