Clinical Value of lncRNA MEG3 in High-Grade Serous Ovarian Cancer.

Marianna Buttarelli,Giovanni Scambia,Enrica Martinelli,Anna Fagotti,Daniela Gallo,Alessandra Ciucci,Gabriele Babini,Pina Baccaro,Marta De Donato,Giuseppina Raspaglio,Tina Pasciuto

doi:10.3390/cancers12040966

Abstract

Long non-coding RNAs (lncRNAs) are emerging as regulators in cancer development and progression, and aberrant lncRNA profiles have been reported in several cancers. Here, we evaluated the potential of using the maternally expressed gene 3 (MEG3) tissue level as a prognostic marker in high-grade serous ovarian cancer (HGSOC), the most common and deadliest gynecologic malignancy. To the aim of the study, we measured MEG3 transcript levels in 90 pre-treatment peritoneal biopsies. We also investigated MEG3 function in ovarian cancer biology. We found that high MEG3 expression was independently associated with better progression-free (p = 0.002) and overall survival (p = 0.01). In vitro and in vivo preclinical studies supported a role for MEG3 as a tumor suppressor in HGSOC, possibly through modulation of the phosphatase and tensin homologue (PTEN) network. Overall, results from this study demonstrated that decreased MEG3 is a hallmark for malignancy and tumor progression in HGSOC.

Highlights

Ovarian cancer is the deadliest gynecologic malignancy
Our results demonstrate that maternally expressed gene 3 (MEG3) may be a useful prognostic marker for high-grade serous ovarian cancer (HGSOC) patients, and its inactivation participates in the regulation of cancer cell development and progression
To evaluate the prognostic potential of MEG3 in HGSOC, we assessed its expression in 90 peritoneal biopsies and correlated results with progression-free survival (PFS) and overall survival (OS) in univariate and multivariate analyses, adjusted for clinicopathological parameters

Summary

Introduction

Ovarian cancer is the deadliest gynecologic malignancy. Nearly 295,000 women were estimated to have been diagnosed with ovarian cancer and 185,000 to have died from the disease in 2018, with rates varying across the world [1]. The disease typically presents at advanced stage (III–IV) where the 5 year survival is around 30%. Few cases (15%) are diagnosed with localized tumor (stage I), with a 5 year survival rate of 92% [2]. High-grade serous ovarian cancer (HGSOC), known as high-grade serous carcinoma, is estimated to be 50–60% of all ovarian malignancies, and advanced-stage HGSOC represents nearly a half of all epithelial ovarian cancer [3]. Limited understanding of disease biology and lack of screening tests to diagnose disease early, along with insufficient treatment approaches, represent the main problems concerning HGSOC [4].

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