Research Article

The Correlation between EGFR and Androgen Receptor Pathways: A Novel Potential Prognostic Marker in Gastric Cancer

Author(s):

Shahrzad S. Fard, Kioomars Saliminejad, Masoud Sotoudeh, Niloofar Soleimanifard, Shaghayegh Kouchaki, Mansour Yazdanbod, Habibollah Mahmoodzadeh, Ardeshir Ghavamzadeh, Reza Malekzadeh, Bahram Chahardouli, Kamran Alimoghaddam* and Seyed H. Ghaffari*   Pages 2097 - 2107 ( 11 )

Abstract:

Background: Despite worthy biologic rationale and numerous studies introducing therapeutic strategies targeting Epidermal Growth Factor Receptor (EGFR), phase III clinical trials have claimed that these current anti-EGFR agents did not significantly improve overall survival of Gastric Cancer (GC) patients. Therefore, to discover flawless candidates of anti-EGFR therapy and ideal prognostic markers, innovative studies are warranted.

Methods: The aim of this study was to assess the expression profile of EGFR in GC, adjacent non-tumor and normal gastric tissues by qRT-PCR, investigating the association of EGFR expression with clinicopathological features, evaluating possible molecular interaction between EGFR and Androgen Receptor (AR), and elucidating novel prognostic marker using Cox regression model.

Results: Among 60 GC patients, 70% (42/60) overexpressed EGFR relative to normal gastric tissues. EGFR overexpression was significantly correlated with the AR overexpression in GC patients. Although EGFR overexpression was remarkably associated with unfavorable outcomes (HR= 4.067, 95% CI= 1.228-13.467, p= 0.022), it was not an independent prognostic factor adjusted for other variables. However, we provided evidences that simultaneous evaluation of EGFR and AR expression, could independently predict the outcome of GC patients and could use as a precise prognostic marker. Moreover, it was revealed that induction or inhibition of AR signaling could alter the mRNA expression of EGFR in GC cell lines.

Conclusion: By targeting AR and EGFR using a potent AR inhibitor such as Enzalutamide, we postulate the possible crosstalk between EGFR and AR pathways in GC. Moreover, our study provided evidences elucidating a novel promising marker, simultaneous evaluation of EGFR and AR expression, which could properly predict prognosis of gastric cancer patients.

Keywords:

Epidermal Growth Factor Receptor (EGFR), Androgen Receptor (AR), Gastric Cancer (GC), targeted therapy, prognostic marker, Enzalutamide (ENZ).

Affiliation:

Hematology, Oncology and Stem Cell Transplantation Research Institute, School of Medicine, Tehran University of Medical Sciences, Tehran, Hematology, Oncology and Stem Cell Transplantation Research Institute, School of Medicine, Tehran University of Medical Sciences, Tehran, Digestive Oncology Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Hasheminejad Kidney Center, Iran University of Medical Science, Tehran, Hematology, Oncology and Stem Cell Transplantation Research Institute, School of Medicine, Tehran University of Medical Sciences, Tehran, Department of Surgery, Madaen Hospital, Tehran, Department of Surgical Oncology, Cancer Institute, Imam Khomeini Hospital Complex, University of Medical Sciences, Tehran, Hematology, Oncology and Stem Cell Transplantation Research Institute, School of Medicine, Tehran University of Medical Sciences, Tehran, Digestive Oncology Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Hematology, Oncology and Stem Cell Transplantation Research Institute, School of Medicine, Tehran University of Medical Sciences, Tehran, Hematology, Oncology and Stem Cell Transplantation Research Institute, School of Medicine, Tehran University of Medical Sciences, Tehran, Hematology, Oncology and Stem Cell Transplantation Research Institute, School of Medicine, Tehran University of Medical Sciences, Tehran

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