HGF/c-Met axis drives cancer aggressiveness in the neo-adjuvant setting of ovarian cancer

Oncotarget. 2014 Jul 15;5(13):4855-67. doi: 10.18632/oncotarget.2049.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Chemotherapy, Adjuvant
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Hepatocyte Growth Factor / genetics*
  • Hepatocyte Growth Factor / metabolism
  • Humans
  • Immunohistochemistry / methods
  • Kaplan-Meier Estimate
  • MicroRNAs / genetics
  • Middle Aged
  • Neoadjuvant Therapy
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / pathology
  • Proto-Oncogene Proteins c-met / genetics*
  • Proto-Oncogene Proteins c-met / metabolism
  • Retrospective Studies
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tissue Array Analysis
  • Treatment Outcome

Substances

  • HGF protein, human
  • MIRN193 microRNA, human
  • MicroRNAs
  • Hepatocyte Growth Factor
  • Proto-Oncogene Proteins c-met