Title:The Correlation between EGFR and Androgen Receptor Pathways: A Novel Potential Prognostic Marker in Gastric Cancer
Volume: 19
Issue: 17
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*Seyed H. Ghaffari*
Affiliation:
- Hematology, Oncology and Stem Cell Transplantation Research Institute, School of Medicine, Tehran University of Medical Sciences, Tehran,Iran
- Hematology, Oncology and Stem Cell Transplantation Research Institute, School of Medicine, Tehran University of Medical Sciences, Tehran,Iran
Keywords:
Epidermal Growth Factor Receptor (EGFR), Androgen Receptor (AR), Gastric Cancer (GC), targeted therapy, prognostic
marker, Enzalutamide (ENZ).
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.
