title: MiRNA landscape in stage I epithelial ovarian cancer defines the histotype specificities.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.affiliation: Department of Biology, University of Padova, Via U.Bassi, Padova, Italy.
authors.forename: Enrica
authors.initials: E
authors.lastname: Calura
authors.forename: Robert
authors.initials: R
authors.lastname: Fruscio
authors.forename: Lara
authors.initials: L
authors.lastname: Paracchini
authors.forename: Eliana
authors.initials: E
authors.lastname: Bignotti
authors.forename: Antonella
authors.initials: A
authors.lastname: Ravaggi
authors.forename: Paolo
authors.initials: P
authors.lastname: Martini
authors.forename: Gabriele
authors.initials: G
authors.lastname: Sales
authors.forename: Luca
authors.initials: L
authors.lastname: Beltrame
authors.forename: Luca
authors.initials: L
authors.lastname: Clivio
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Ceppi
authors.forename: Mariacristina
authors.initials: M
authors.lastname: Di Marino
authors.forename: Ilaria
authors.initials: I
authors.lastname: Fuso Nerini
authors.forename: Laura
authors.initials: L
authors.lastname: Zanotti
authors.forename: Duccio
authors.initials: D
authors.lastname: Cavalieri
authors.forename: Giorgio
authors.initials: G
authors.lastname: Cattoretti
authors.forename: Patrizia
authors.initials: P
authors.lastname: Perego
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Milani
authors.forename: Dionyssios
authors.initials: D
authors.lastname: Katsaros
authors.forename: Germana
authors.initials: G
authors.lastname: Tognon
authors.forename: Enrico
authors.initials: E
authors.lastname: Sartori
authors.forename: Sergio
authors.initials: S
authors.lastname: Pecorelli
authors.forename: Costantino
authors.initials: C
authors.lastname: Mangioni
authors.forename: Maurizio
authors.initials: M
authors.lastname: D'Incalci
authors.forename: Chiara
authors.initials: C
authors.lastname: Romualdi
authors.forename: Sergio
authors.initials: S
authors.lastname: Marchini
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D000077216:Carcinoma, Ovarian Epithelial; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D046228:Microarray Analysis; D009367:Neoplasm Staging; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs