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BMC Cancer
Published in: BMC Cancer 1/2017

Open Access 01-12-2017 | Research article

MAL gene overexpression as a marker of high-grade serous ovarian carcinoma stem-like cells that predicts chemoresistance and poor prognosis

Authors: Laura Zanotti, Chiara Romani, Laura Tassone, Paola Todeschini, Renata Alessandra Tassi, Elisabetta Bandiera, Giovanna Damia, Francesca Ricci, Laura Ardighieri, Stefano Calza, Sergio Marchini, Luca Beltrame, Germana Tognon, Maurizio D’Incalci, Sergio Pecorelli, Enrico Sartori, Franco Odicino, Antonella Ravaggi, Eliana Bignotti

Published in: BMC Cancer | Issue 1/2017

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Abstract

Background

The existence of cancer stem cells (CSCs) within a tumor bulk has been demonstrated for many solid tumors including epithelial ovarian carcinoma (EOC). CSCs have been associated to tumor invasion, metastasis and development of chemoresistant recurrences. In this context, we aim to characterize EOC CSCs from the molecular point of view in order to identify potential biomarkers associated with chemoresistance.

Methods

We isolated a population of cells with stem-like characteristics (OVA-BS4 spheroids) from a primary human EOC cell line under selective conditions. OVA-BS4 spheroids were characterized for drug response by cytotoxicity assays and their molecular profile was investigated by microarray and RT-qPCR. Finally, we performed a gene expression study in a cohort of 74 high-grade serous EOC (HGSOC) patients by RT-qPCR.

Results

Spheroids exhibited properties of self-renewal and a pronounced expression of well-known stem cell genes. Moreover, they demonstrated greater resistance towards several anticancer drugs compared to parent cell line, consistent with their higher ABCG2 gene expression. From microarray studies MAL (T-cell differentiation protein) emerged as the most up-regulated gene in spheroids, compared to parent cell line. In HGSOC patients, MAL was significantly overexpressed in platinum-resistant compared to platinum-sensitive patients and resulted as an independent prognostic marker of survival.

Conclusions

This investigation provides an important contribution to the identification of molecular markers of ovarian CSCs and chemoresistance. Successful translation of molecular findings would lead to a better comprehension of the mechanisms triggering chemoresistant recurrences, to the individuation of novel therapeutic targets and to the personalization of treatment regimens.
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Metadata
Title
MAL gene overexpression as a marker of high-grade serous ovarian carcinoma stem-like cells that predicts chemoresistance and poor prognosis
Authors
Laura Zanotti
Chiara Romani
Laura Tassone
Paola Todeschini
Renata Alessandra Tassi
Elisabetta Bandiera
Giovanna Damia
Francesca Ricci
Laura Ardighieri
Stefano Calza
Sergio Marchini
Luca Beltrame
Germana Tognon
Maurizio D’Incalci
Sergio Pecorelli
Enrico Sartori
Franco Odicino
Antonella Ravaggi
Eliana Bignotti
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2017
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-017-3334-1

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