lncRNAs as Novel Indicators of Patients' Prognosis in Stage I Epithelial Ovarian Cancer: A Retrospective and Multicentric Study.
Purpose:Stage I epithelial ovarian cancer (EOC) represents about 10% of all EOCs and is characterized by good prognosis with fewer than 20% of patients relapsing. As it occurs less frequently than advanced-stage EOC, its molecular features have not been thoroughly investigated. We have demonstrated that in stage I EOCmiR-200c-3pcan predict patients' outcome. In the present study, we analyzed the expression of long non-coding RNAs (lncRNA) to enable potential definition of a non-coding transcriptional signature with prognostic relevance for stage I EOC.Experimental Design:202 snap-frozen stage I EOC tumor biopsies, 47 of which relapsed, were gathered together from three independent tumor tissue collections and subdivided into a training set (n= 73) and a validation set (n= 129). Median follow up was 9 years. LncRNAs' expression profiles were correlated in univariate and multivariate analysis with overall survival (OS) and progression-free survival (PFS).Results:The expression oflnc-SERTAD2-3, lnc-SOX4-1, lnc-HRCT1-1, andPVT1was associated in univariate and multivariate analyses with relapse and poor outcome in both training and validation sets (P< 0.001). Using the expression profiles ofPVT1, lnc-SERTAD2-3, andmiR-200c-3psimultaneously, it was possible to stratify patients into high and low risk. The OS for high- and low-risk individuals are 36 and 123 months, respectively (OR, 15.55; 95% confidence interval, 3.81-63.36).Conclusions:We have identified a non-coding transcriptional signature predictor of survival and biomarker of relapse for stage I EOC.Clin Cancer Res; 23(9); 2356-66. ©2016 AACR.
Department of Biology, University of Padova, Padova, Italy.
Paolo
P
Martini
Department of Oncology, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", Milano, Italy.
Lara
L
Paracchini
Department of Oncology, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", Milano, Italy.
Giulia
G
Caratti
Cancer Genomics Laboratory, Edo and Elvo Tempia Valenta Foundation, Biella, Italy.
Maurizia
M
Mello-Grand
Clinic of Obstetrics and Gynaecology, University of Milano-Bicocca, San Gerardo Hospital, Monza, Italy.
Robert
R
Fruscio
Department of Oncology, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", Milano, Italy.
Luca
L
Beltrame
Department of Biology, University of Padova, Padova, Italy.
Enrica
E
Calura
Department of Biology, University of Padova, Padova, Italy.
Gabriele
G
Sales
Division of Gynaecologic Oncology, "Angelo Nocivelli" Institute of Molecular Medicine, University of Brescia, Brescia, Italy.
Antonella
A
Ravaggi
Division of Gynaecologic Oncology, "Angelo Nocivelli" Institute of Molecular Medicine, University of Brescia, Brescia, Italy.
Eliana
E
Bignotti
Department of Obstetrics and Gynecology, University of Brescia, Brescia, Italy.
Franco E
FE
Odicino
Department of Obstetrics and Gynecology, University of Brescia, Brescia, Italy.
Enrico
E
Sartori
Pathology Unit University of Milan-Bicocca, San Gerardo Hospital, Monza, Italy.
Patrizia
P
Perego
Azienda Ospedaliero-Universitaria Città della Salute, Presidio S Anna e Department of Surgical Science, Gynecology, University of Torino, Torino, Italy.
Dionyssios
D
Katsaros
Department of Oncology, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", Milano, Italy.
Ilaria
I
Craparotta
Cancer Genomics Laboratory, Edo and Elvo Tempia Valenta Foundation, Biella, Italy.
Giovanna
G
Chiorino
Department of Biology, University of Padova, Padova, Italy.|C.R.I.B.I. Biotechnology Centre, University of Padova, Padova, Italy.
Stefano
S
Cagnin
Department of Oncology, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", Milano, Italy.
Laura
L
Mannarino
Clinic of Obstetrics and Gynaecology, University of Milano-Bicocca, San Gerardo Hospital, Monza, Italy.
Lorenzo
L
Ceppi
P.O.A Manzoni, Lecco, Italy.
Costantino
C
Mangioni
Cancer Genomics Laboratory, Edo and Elvo Tempia Valenta Foundation, Biella, Italy.
Chiara
C
Ghimenti
Department of Oncology, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", Milano, Italy. maurizio.dincalci@marionegri.it.
Maurizio
M
D'Incalci
Department of Oncology, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", Milano, Italy.
Sergio
S
Marchini
Department of Biology, University of Padova, Padova, Italy.
Chiara
C
Romualdi
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D000077216:Carcinoma, Ovarian Epithelial; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009367:Neoplasm Staging; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D062085:RNA, Long Noncoding / Q000235:genetics*; D012189:Retrospective Studies
D014408:Biomarkers, Tumor; D062085:RNA, Long Noncoding