title: Circulating miRNA landscape identifies miR-1246 as promising diagnostic biomarker in high-grade serous ovarian carcinoma: A validation across two independent cohorts.
abstract: High-grade serous ovarian carcinoma (HGSOC) is the most lethal gynecologic neoplasm, with five-year survival rate below 30%. Early disease detection is of utmost importance to improve HGSOC cure rate. Sera from 168 HGSOC patients and 65 healthy controls were gathered together from two independent collections and stratified into a training set, for miRNA marker identification, and a validation set, for data validation. An innovative statistical approach for microarray data normalization was developed to identify differentially expressed miRNAs. Signature validation in both the training and validation sets was performed by quantitative Real Time PCR (RT-qPCR). In both the training and validation sets, miR-1246, miR-595 and miR-2278 emerged significantly over expressed in the sera of HGSOC patients compared to healthy controls. Receiver Operating Characteristic curve analysis revealed miR-1246 as the best diagnostic biomarker, with a sensitivity of 87%, a specificity of 77% and an accuracy of 84%. This study is the first step in the identification of circulating miRNAs with diagnostic relevance for HGSOC. According to its specificity and sensitivity, circulating miR-1246 levels are worthy to be further investigated as potential diagnostic biomarker for HGSOC.
authors.affiliation: Department of Obstetrics and Gynecology, "Angelo Nocivelli" Institute of Molecular Medicine, University of Brescia, Brescia, Italy; Doctorate School of Molecular and Translational Medicine, University of Milano, Milano, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Todeschini
authors.affiliation: Department of Biology, University of Padova, Padova, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Salviato
authors.affiliation: Department of Oncology, IRCCS - "Mario Negri" Institute for Pharmacological Research, Milano, Italy.
authors.forename: Lara
authors.initials: L
authors.lastname: Paracchini
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine - DIMES, University of Bologna, Bologna, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Ferracin
authors.affiliation: Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Petrillo
authors.affiliation: Department of Obstetrics and Gynecology, "Angelo Nocivelli" Institute of Molecular Medicine, University of Brescia, Brescia, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Zanotti
authors.affiliation: Division of Obstetrics and Gynecology, ASST Spedali Civili di Brescia, Brescia, Italy.
authors.forename: Germana
authors.initials: G
authors.lastname: Tognon
authors.affiliation: Department of Obstetrics and Gynecology, University of Brescia, Brescia, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Gambino
authors.affiliation: Department of Biology, University of Padova, Padova, Italy.
authors.forename: Enrica
authors.initials: E
authors.lastname: Calura
authors.affiliation: Department of Oncology, IRCCS - "Mario Negri" Institute for Pharmacological Research, Milano, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Caratti
authors.affiliation: Department of Biology, University of Padova, Padova, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Martini
authors.affiliation: Department of Oncology, IRCCS - "Mario Negri" Institute for Pharmacological Research, Milano, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Beltrame
authors.affiliation: Department of Biology, University of Padova, Padova, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Maragoni
authors.affiliation: Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Gallo
authors.affiliation: Department of Obstetrics and Gynecology, University of Brescia, Brescia, Italy.
authors.forename: Franco E
authors.initials: FE
authors.lastname: Odicino
authors.affiliation: Department of Obstetrics and Gynecology, University of Brescia, Brescia, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Sartori
authors.affiliation: Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Scambia
authors.affiliation: Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Negrini
authors.affiliation: Department of Obstetrics and Gynecology, "Angelo Nocivelli" Institute of Molecular Medicine, University of Brescia, Brescia, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Ravaggi
authors.affiliation: Department of Oncology, IRCCS - "Mario Negri" Institute for Pharmacological Research, Milano, Italy. Electronic address: maurizio.dincalci@marionegri.it.
authors.forename: Maurizio
authors.initials: M
authors.lastname: D'Incalci
authors.affiliation: Department of Oncology, IRCCS - "Mario Negri" Institute for Pharmacological Research, Milano, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Marchini
authors.affiliation: Division of Obstetrics and Gynecology, ASST Spedali Civili di Brescia, Brescia, Italy.
authors.forename: Eliana
authors.initials: E
authors.lastname: Bignotti
authors.affiliation: Department of Biology, University of Padova, Padova, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Romualdi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D015331:Cohort Studies; D018284:Cystadenocarcinoma, Serous / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D005260:Female; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D060787:Neoplasm Grading; D010051:Ovarian Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D015203:Reproducibility of Results; D012189:Retrospective Studies
chemical_list: D014408:Biomarkers, Tumor; C577700:MIRN1246 microRNA, human; D035683:MicroRNAs
keywords: Diagnosis; High-grade serous ovarian carcinoma; Microarray; Serum miRNA; Tumor marker