Profiling of discrete gynecological cancers reveals novel transcriptional modules and common features shared by other cancer types and embryonic stem cells

Kalliopi I. Pappa, Alexander Polyzos, Jasmine Jacob-Hirsch, Ninette Amariglio, George D. Vlachos, Dimitrios Loutradis, Nicholas P. Anagnou

Research output: Contribution to journalArticlepeer-review

57 Scopus citations

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.

Original languageEnglish
Article numbere0142229
JournalPLoS ONE
Volume10
Issue number11
DOIs
StatePublished - 1 Nov 2015
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2015 Pappa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding

This study was funded by the Oncology Program of the Central Council of Health of the Ministry of Health, Grant No. 70-3-9209 and by the Empirikion Foundation, Grant No. 70-3-7345 to Nicholas P. Anagnou, 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 Kalliopi I. Pappa. The authors wish to thank Dr S. Markaki for expert advice and V. Pavlou for excellent technical assistance.

FundersFunder number
Empirikion Foundation70-3-7345
European Union’s European Social Fund
National Strategic Reference Framework70-3-11830
Ministerio de Sanidad, Consumo y Bienestar Social70-3-9209
European Social Fund

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