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Cells. 2019 Dec 1;8(12). pii: E1554. doi: 10.3390/cells8121554.

Transcriptional Characterization of Stage I Epithelial Ovarian Cancer: A Multicentric Study.

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Department of Biology, University of Padova, 35121 Padua, Italy.
Department of Cellular, Computational and Integrative Biology-CIBIO, University of Trento, 38123 Povo Trento, Italy.
Department of Oncology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 20156 Milano, Italy.
Unit of Biological Adaptation and Ageing UMR8256, Institute of Biology Paris-Seine, Sorbonne University, 75005 Paris, France.
Clinic of Obstetrics and Gynaecology, University of Milano-Bicocca, San Gerardo Hospital, 20900 Monza, Italy.
Department of Surgical Science and Gynecology, Azienda Ospedaliero Universitaria, Città della Salute, presidio S.Anna, University of Torino, 10126 Torino, Italy.
Division of Obstetrics and Gynecology, ASST Spedali Civili di Brescia, 25123 Brescia, Italy.
Angelo Nocivelli Institute of Molecular Medicine, University of Brescia and ASST-Spedali Civili of Brescia, 25123 Brescia, Italy.
Department of Clinical and Experimental Sciences, Division of Obstetrics and Gynecology, University of Brescia, 25123 Brescia, Italy.


Stage I epithelial ovarian cancer (EOC) represents about 10% of all EOCs. It is characterized by a complex histopathological and molecular heterogeneity, and it is composed of five main histological subtypes (mucinous, endometrioid, clear cell and high, and low grade serous), which have peculiar genetic, molecular, and clinical characteristics. As it occurs less frequently than advanced-stage EOC, its molecular features have not been thoroughly investigated. In this study, using in silico approaches and gene expression data, on a multicentric cohort composed of 208 snap-frozen tumor biopsies, we explored the subtype-specific molecular alterations that regulate tumor aggressiveness in stage I EOC. We found that single genes rather than pathways are responsible for histotype specificities and that a cAMP-PKA-CREB1 signaling axis seems to play a central role in histotype differentiation. Moreover, our results indicate that immune response seems to be, at least in part, involved in histotype differences, as a higher immune-reactive behavior of serous and mucinous samples was observed with respect to other histotypes.


cancer histotypes; gene expressions; pathways; stage I ovarian cancer

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