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

I期上皮性卵巢癌的转录组特征:一项多中心研究

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作者:Enrica Calura ,Matteo Ciciani ,Andrea Sambugaro ,Lara Paracchini ,Giuseppe Benvenuto ,Salvatore Milite ,Paolo Martini ,Luca Beltrame ,Flaminia Zane ,Robert Fruscio ,Martina Delle Marchette ,Fulvio Borella ,Germana Tognon ,Antonella Ravaggi ,Dionyssios Katsaros ,Eliana Bignotti ,Franco Odicino ,Maurizio D'Incalci ,Sergio Marchini ,Chiara Romualdi

Abstract

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. Keywords: cancer histotypes; gene expressions; pathways; stage I ovarian cancer.

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