HGF/c-Met axis drives cancer aggressiveness in the neo-adjuvant setting of ovarian cancer
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Marisa Mariani1,2, Mark McHugh1, Marco Petrillo2, Steven Sieber1, Shiquan He1, Mirko Andreoli1,2, Zheyang Wu3, Paul Fiedler1, Giovanni Scambia2,4, Shohreh Shahabi1,* and Cristiano Ferlini1,4,*
1 Danbury Hospital Research Institute, Danbury, CT, USA
2 Department of Gynecology, Catholic University of the Sacred Heart, Rome, Italy
3 Department of Mathematical Sciences, Worcester Polytechnic Institute, Worcester, MA, USA
4 Department of Oncology, Jean Paul IInd Research Foundation, Campobasso, Italy
* These Authors equally contributed to this work
Cristiano Ferlini, email:
Keywords: HGF, Met, Ovarian Cancer
Received: March 31, 2014 Accepted: May 30, 2014 Published: June 1, 2014
Ovarian cancer is the most lethal gynecologic malignancy. Recently, NACT (Neo Adjuvant Chemotherapy) has been tested as alternative approach for the management of ovarian cancer patients. A biological predictor helpful in selecting patients for NACT would be desirable. This study was aimed at identifying actionable mechanisms of resistance to NACT.
Expression of a panel of microRNAs was screened in a discovery set of 85 patients. Analysis of the potential targets was conducted in the same RNAs by calculating significant correlations between microRNAs and genes. Quantitative fluorescent immunohistochemistry was employed in a validation set of 109 patients.
MiR-193a-5p was significantly overexpressed in the NACT setting. Analysis of its potential targets demonstrated that this microRNA is also significantly correlated with HGF and MET genes. Analysis of protein expression in samples taken before and after NACT demonstrated that both HGF and c-Met are increased after NACT. Patients who relapse shortly after NACT exhibited the highest relative basal expression of both HGF and c-Met, while the opposite phenomenon was observed in the best responders.
Mir-193a-5p, HGF and c-Met expression may help select eligible patients for this modality of treatment. Moreover, inhibitors of this pathway may improve the efficacy of NACT.
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