title: HGF/c-Met axis drives cancer aggressiveness in the neo-adjuvant setting of ovarian cancer.
abstract: 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.
authors: Danbury Hospital Research Institute, Danbury, CT, USA; Department of Gynecology, Catholic University of the Sacred Heart, Rome, Italy.
authors: Marisa
authors: M
authors: Mariani
authors: Mark
authors: M
authors: McHugh
authors: Marco
authors: M
authors: Petrillo
authors: Steven
authors: S
authors: Sieber
authors: Shiquan
authors: S
authors: He
authors: Mirko
authors: M
authors: Andreoli
authors: Zheyang
authors: Z
authors: Wu
authors: Paul
authors: P
authors: Fiedler
authors: Giovanni
authors: G
authors: Scambia
authors: Shohreh
authors: S
authors: Shahabi
authors: Danbury Hospital Research Institute, Danbury, CT, USA; Department of Oncology, Jean Paul IInd Research Foundation, Campobasso, Italy.
authors: Cristiano
authors: C
authors: Ferlini
mesh_terms: D045744:Cell Line, Tumor; D017024:Chemotherapy, Adjuvant; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D017228:Hepatocyte Growth Factor / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D053208:Kaplan-Meier Estimate; D035683:MicroRNAs / Q000235:genetics; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics* / Q000378:metabolism; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D046888:Tissue Array Analysis; D016896:Treatment Outcome
chemical_list: C066855:HGF protein, human; C546818:MIRN193 microRNA, human; D035683:MicroRNAs; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met