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Page 12 of 27 J Cancer Metastasis Treat 2019;5:5 I http://dx.doi.org/10.20517/2394-4722.2018.108

Introduction: IL-6, a pro-inflammatory cytokine produced by cancer-associated fibroblasts, increases the
proliferative and invasive properties of ovarian cancer cells. Glucose metabolism is altered in ovarian cancer
cells and permits fast proliferation and survival. Resveratrol (RV) is a naturally occurring polyphenol with
the potential to inhibit cancer cell migration.

Results: Here, we found that IL-6 enhances ovarian cancer cell migration, while RV and deprivation of
glucose reduce cell motility. In particular, IL-6 stimulates glucose uptake along with cell migration, while
RV abrogates this effect through the reduction of GLUT1 plasma membrane translocation and glucose
internalization. Further, the cells exposed to IL-6 at the migration front show an increased expression of
N-cadherin over E-cadherin, and this effect is reverted by RV exposure. Accordingly, the expression of
TWIST1, a regulator of epithelial-to-mesenchymal transition (EMT), is reduced by RV and deprivation of
glucose. Transcriptomic and microRNomic analyses revealed that RV up-regulates a subset of miRNAs
that have several glucose metabolism regulators as targets. In particular, we found that RV abrogates the
transcription of ZEB1, Hexokinase 2 and FOXM1.

Conclusion: Our data indicate that RV counteracts glucose metabolism negatively impinging on ovarian
cancer cell migration induced by IL-6.

17. FXYD5 is a predictor of short-term survival in high-grade serous ovarian carcinoma

2
1,
3
3
Antonella Ravaggi 1,2, *, Renata A Tassi *, Angela Gambino , Laura Ardighieri , Mattia Bugatti ,
Chiara Romani , Paola Todeschini , Laura Zanotti , Francesco Gebbia , Elisa Picardo ,
4
2
5
1
1
2
1,6
7
5
Dionyssios Katsaros , Eliana Bignotti , Chiara Romualdi , Enrico Sartori , Franco Odicino 2
1 “A. Nocivelli” Institute of Molecular Medicine, ASST Spedali Civili of Brescia, Brescia 25123, Italy.
2 Division of Obstetrics and Gynecology, University of Brescia, Brescia 25121, Italy.
3 Department of Pathology, ASST Spedali Civili of Brescia, Brescia 25123, Italy.
4 Department of Molecular and Translational Medicine, University of Brescia, Brescia 25121, Italy.
5 Department of Surgical Sciences, Gynecologic Oncology, Città della Salute and S Anna Hospital, University of
Turin, Turin 10126, Italy.
6 Division of Obstetrics and Gynecology, ASST Spedali Civili of Brescia, Brescia 25123, Italy.
7 Department of Biology, University of Padova, Padova 35122, Italy.
*Equal contribution.
Introduction: High-grade serous ovarian carcinoma (HGSOC) is generally associated with a very dismal
prognosis. Nevertheless, patients with similar clinicopathological characteristics can have markedly different
clinical outcomes. We aim to identify the molecular determinants influencing survival by comparing the
gene expression patterns of two patient cohorts characterized by extreme overall survival.

Experimental model: We determined the gene expression profiles of 12 HGSOC long-term and 27 short-
term survivors (training set) by microarray chips. By a generalized linear model with cross-validation,
we generated a prognostic gene signature that was further evaluated on the entire “The Cancer Genome
Atlas” (TCGA) ovarian cancer dataset. The resulting genes were then verified on an independent cohort of
29 HGSOC flash frozen samples (validation set) by RT-qPCR, and in a panel of 38 formalin fixed paraffin
embedded HGSOC tissues by immunohistochemistry (IHC).

Results: We identified a ten-gene prognostic signature able to correctly assign 98% of patients of the training
set within their survival class. By “in silico” validation on TCGA microarray dataset, we confirmed the
overexpression in short term survivors of FXYD domain containing ion transport regulator 5 (FXYD5),