Beclin 1 activation enhances chemosensitivity and predicts a favorable outcome for primary duodenal adenocarcinoma

Abstract

We and others had proven that hypoxia-induced autophagy was essential to regulate cancer cell destiny under anticancer therapeutic stress. Here, we addressed the clinicopathologic effect of HIF-1α and autophagic Beclin 1 in primary duodenal adenocarcinoma (PDA). HIF-1α and Beclin 1 expression level were semi-quantitatively evaluated using tissue microarrays and immunohistochemistry (IHC) staining in 141 PDA patients. Among these patients, 77 acted as training set to select HIF-1α and Beclin 1 IHC cutoff score for patient outcome, and 64 cases were used as testing set to evaluate their prognostic effect. We found that Beclin 1 was cytoplasmic overexpressed, defined by training set fixed cutoff point, in 49.6 % PDA tissue, compared to 46.8 % patients had HIF-1α high expression. In testing set, Beclin 1 overexpression predicted a superior 5-year overall survival (OS) in both univariate (P = 0.010) and multivariate (P = 0.017) analyses. However, we did not detect any correlation between HIF-1α level and patient prognosis (P = 0.989). Significantly, among Beclin 1 overexpressed patients, radical surgery plus adjuvant chemotherapy had a 23.1-month OS improvement than given radical surgery alone (59.2 vs 36.1 months; P = 0.01). For Beclin 1 lowly expressed patients, radical surgery plus adjuvant chemotherapy and given radical surgery alone had the similar OS (P = 0.283). Contrary to previous studies, we failed to detect any correlation between Beclin 1 and HIF-1α levels in PDA (correlation coefficient 0.217, P = 0.099). In conclusions, our results confirmed that Beclin 1 was a favorable prognostic biomarker for PDA, and might be used to identify particular patients for more selective therapy.