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Anticancer Agents Med Chem. 2019 Sep 30. doi: 10.2174/1871520619666190930142820. [Epub ahead of print]

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

Author information

1
Hematology, Oncology and Stem Cell Transplantation Research Institute, School of Medicine, Tehran University of Medical Sciences, Tehran. Iran.
2
Digestive Oncology Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran. Iran.
3
Hasheminejad Kidney Center, Iran University of Medical Science, Tehran. Iran.
4
Department of Surgery, Madaen Hospital, Tehran. Iran.
5
Department of Surgical Oncology, Cancer Institute, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran. Iran.

Abstract

BACKGROUND:

Despite of 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 assessing 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 outcome (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 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:

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

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