The clinical impact of angiotensin-(1–7)/mitochondrial assembly receptor axis in esophageal squamous cell carcinoma patients receiving curative esophagectomy

Abstract

Background: Mitochondrial assembly receptor (MasR), a receptor of angiotensin-(1–7), plays an important role in the anti-cancer effect of the peptide hormone. The aim of the current study was to evaluate the crucial role of angiotensin-(1–7)/MasR axis in esophageal squamous cell carcinoma (ESCC) patients who received curative esophagectomy. Methods: The immunohistochemistry of MasR in 90 ESCC patients, including 52 patients with MasR overexpression and 38 patients with low MasR expression, was examined and correlated with their treatment outcomes. Two ESCC cell lines, TE11 and KYSE270, were treated with angiotensin-(1–7) to explore the biological function of MasR. Results: A higher percentage of patients in the low MasR expression group experienced tumor recurrence than those in the MasR overexpression group (76% versus 54%, P = 0.029). Patients below 60 years of age and having early T status and negative pathologic N status were found to have significantly better disease-free survival (DFS) and overall survival (OS). Additionally, patients with MasR overexpression had higher DFS (88.1 months versus 50.0 months, p = 0.023) and OS (129.4 months versus 67.5 months, p = 0.028) relative to those with low MasR expression, although there was no significant difference in multivariable analysis. In vitro, these cell lines were treated with angiotensin-(1–7) and the results demonstrated that angiotensin-(1–7) could inhibit the growth of ESCC tumor cells in a dose-dependent manner. Conclusion: Low expression of MasR may be associated with poor prognosis in ESCC patients receiving curative esophagectomy. Further cohort study with larger population, or a prospective study is warranted to validate this finding. Keywords: Angiotensin-(1–7), Mitochondrial assembly receptor, Esophageal cancer, Squamous cell carcinoma, Esophagectomy