MiRNA landscape in stage I epithelial ovarian cancer defines the histotype specificities.

Abstract

PURPOSE:

Epithelial ovarian cancer (EOC) is one of the most lethal gynecologic diseases, with survival rate virtually unchanged for the past 30 years. EOC comprises different histotypes with molecular and clinical heterogeneity, but up till now the present gold standard platinum-based treatment has been conducted without any patient stratification. The aim of the present study is to generate microRNA (miRNA) profiles characteristic of each stage I EOC histotype, to identify subtype-specific biomarkers to improve our understanding underlying the tumor mechanisms.

EXPERIMENTAL DESIGN:

A collection of 257 snap-frozen stage I EOC tumor biopsies was gathered together from three tumor tissue collections and stratified into independent training (n = 183) and validation sets (n = 74). Microarray and quantitative real-time PCR (qRT-PCR) were used to generate and validate the histotype-specific markers. A novel dedicated resampling inferential strategy was developed and applied to identify the highest reproducible results. mRNA and miRNA profiles were integrated to identify novel regulatory circuits.

RESULTS:

Robust miRNA markers for clear cell and mucinous histotypes were found. Specifically, the clear cell histotype is characterized by a five-fold (log scale) higher expression of miR-30a and miR-30a*, whereas mucinous histotype has five-fold (log scale) higher levels of miR-192/194. Furthermore, a mucinous-specific regulatory loop involving miR-192/194 cluster and a differential regulation of E2F3 in clear cell histotype were identified.

CONCLUSIONS:

Our findings showed that stage I EOC histotypes have their own characteristic miRNA expression and specific regulatory circuits.

• Authors: Enrica Calura, Robert Fruscio, Lara Paracchini, Eliana Bignotti, Antonella Ravaggi, Paolo Martini, Gabriele Sales, Luca Beltrame, Luca Clivio, Lorenzo Ceppi, Mariacristina Di Marino, Ilaria Fuso Nerini, Laura Zanotti, Duccio Cavalieri, Giorgio Cattoretti, Patrizia Perego, Rodolfo Milani, Dionyssios Katsaros, Germana Tognon, Enrico Sartori, Sergio Pecorelli, Costantino Mangioni, Maurizio D'Incalci, Chiara Romualdi, Sergio Marchini
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 19 Issue 15 Pg. 4114-23 (Aug 01 2013) ISSN: 1557-3265 [Electronic] United States
• PMID: 23766361 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: ©2013 AACR.

Chemical References

• Biomarkers, Tumor
• MicroRNAs

Topics

• Biomarkers, Tumor (genetics)
• Carcinoma, Ovarian Epithelial
• Female
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic
• Humans
• MicroRNAs (genetics)
• Microarray Analysis
• Neoplasm Staging
• Neoplasms, Glandular and Epithelial (genetics, pathology)
• Ovarian Neoplasms (genetics, pathology)
• Prognosis