OncoTargets and Therapy (Oct 2020)
Prognostic and Therapeutic Significance of Androgen Receptor in Patients with Gastric Cancer
Abstract
Shahrzad Soleymani Fard,1 Mansour Yazdanbod,2 Masoud Sotoudeh,3 Davood Bashash,4 Habibollah Mahmoodzadeh,5 Kioomars Saliminejad,1 Seyed Asadollah Mousavi,1 Seyed H Ghaffari,1 Kamran Alimoghaddam1 1Hematology, Oncology and Stem Cell Transplantation Research Institute, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; 2Department of Surgery, Madaen Hospital, Tehran, Iran; 3Digestive Oncology Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran; 4Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 5Department of Surgical Oncology, Cancer Institute, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, IranCorrespondence: Kamran Alimoghaddam; Seyed H Ghaffari Hematology, Oncology and Stem Cell Transplantation Research Institute, Shariati Hospital, School of MedicineTehran University of Medical Sciences, North Kargar Avenue, Tehran, IranTel +982184902665Fax +982188004140Email [email protected]; [email protected]: The clinical studies carried out in the last few decades unequivocally introduced activated androgen receptor (AR) as a pathogenic feature of human malignancies which not only endows cancer cells with survival advantage, but also may be exploited for anticancer interventions.Patients and Methods: In this study, we have investigated the expression profile of AR and EMT-related genes in fresh gastric cancer (GC), adjacent nontumor and normal gastric tissues, as well as the effect and molecular mechanisms of AR inhibition in GC cell lines.Results: Amongst 60 GC patients, 66.7% overexpressed AR that was remarkably correlated with the overexpression of Snail, β-catenin, Twist1, and STAT3. AR overexpression was also remarkably associated with unfavorable outcome (HR=3.478, P=0.001); however, multivariate Cox regression analysis indicated that it was not an independent prognostic factor (HR=2.089, P=0.056). This study has investigated simultaneous assessment of AR and EMT-related genes expression and indicated that concurrent overexpression of AR and Snail is an independent unfavorable factor for GC overall survival after adjustment with other variables (HR=2.382, P=0.021). Interestingly, the inhibition of AR signaling by potent AR antagonist enzalutamide suppressed cell growth, migration and invasion of GC cells via regulation of apoptosis-, cell cycle-, and EMT-related gene expressions.Conclusion: Our findings have clinical importance proposing AR as an important prognostic factor involved in GC progression and metastasis, and submit AR inhibition as an appealing therapeutic approach for GC patients, either as a single agent or in a combined-modal strategy.Keywords: androgen receptor, gastric cancer, epithelial-mesenchymal transition, EMT, prognosis, targeted therapy, enzalutamide
