title: 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.
authors.affiliation: Department of Medical Oncology, Third Affiliated Hospital, Sun Yat-sen University, 600 Tianhe Road, Guangzhou, 510630, China. wuxiangy@mail.sysu.edu.cn
authors.forename: Xiang-Yuan
authors.initials: XY
authors.lastname: Wu
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.forename: Qing-Hua
authors.initials: QH
authors.lastname: Cao
authors.forename: Min
authors.initials: M
authors.lastname: Dong
authors.forename: Qu
authors.initials: Q
authors.lastname: Lin
authors.forename: Xin-Juan
authors.initials: XJ
authors.lastname: Fan
authors.forename: Qing
authors.initials: Q
authors.lastname: Xia
authors.forename: Zhan-Hong
authors.initials: ZH
authors.lastname: Chen
authors.forename: Quentin
authors.initials: Q
authors.lastname: Liu
authors.forename: Xiang-Bo
authors.initials: XB
authors.lastname: Wan
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism / Q000401:mortality*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D000071186:Beclin-1; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015153:Blotting, Western; D019008:Drug Resistance, Neoplasm; D004379:Duodenal Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000401:mortality*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D015996:Survival Rate; D046888:Tissue Array Analysis
chemical_list: D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D014408:Biomarkers, Tumor; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008565:Membrane Proteins