title: Low expression of Beclin 1 and elevated expression of HIF-1α refine distant metastasis risk and predict poor prognosis of ER-positive, HER2-negative breast cancer.
abstract: Even though ER-positive, HER2-negative breast tumors represent a subset of breast cancers with a better clinical outcome, approximately 12.7 % of patients in this subgroup ultimately develop cancer-related mortality. Recent studies had confirmed that hypoxia-induced autophagy-related gene Beclin 1 expression might be important for disease progression and be correlated with patient outcome in several tumors. Here, we examined the autophagic Beclin 1 and hypoxic HIF-1α levels in 378 ER-positive, HER2-negative breast cancer patients by immunohistochemistry using tissue microarray. We found that Beclin 1 was highly expressed in normal mammary gland epithelia. In contrast, it was either not expressed or only moderately expressed in 78.0 % of breast adenocarcinoma tissue. Compared to the subset overexpressing Beclin 1, the subset in which Beclin 1 levels were reduced had a poor 5-year overall survival rate (OS, 85.1 % vs. 94.1 %, P = 0.005) and a poor distant metastasis-free survival (DMFS, 79.1 % vs. 89.3 %, P = 0.037). Cox multivariate analysis confirmed that Beclin 1 was indeed an independent prognostic factor for OS and DMFS. Additionally, Beclin 1 positively correlated with HIF-1α expression (r = 0.206, P < 0.001). Importantly, among patients with HIF-1α overexpression, low levels of Beclin 1 predicted a worse OS. Our study confirmed that deficiency of Beclin 1 was a negative prognostic factor for OS and DMFS in ER-positive, HER2-negative breast cancer. The combination of Beclin 1 and HIF-1α refined the risk definition of the patient subset and provided a novel way to identify those with a high risk of relapse.
authors: Department of Medical Oncology, The Third Affiliated Hospital, Sun Yat-sen University, 600 Tianhe Rd, Guangzhou 510630, China.
authors: Min
authors: M
authors: Dong
authors: Xiang-bo
authors: XB
authors: Wan
authors: Zhong Yu
authors: ZY
authors: Yuan
authors: Li
authors: L
authors: Wei
authors: Xin Juan
authors: XJ
authors: Fan
authors: Tian-tian
authors: TT
authors: Wang
authors: Yan Chun
authors: YC
authors: Lv
authors: Xing
authors: X
authors: Li
authors: Zhan-hong
authors: ZH
authors: Chen
authors: Jie
authors: J
authors: Chen
authors: Qu
authors: Q
authors: Lin
authors: Jing-yun
authors: JY
authors: Wen
authors: Xiao-kun
authors: XK
authors: Ma
authors: Quentin
authors: Q
authors: Liu
authors: Xiang Yuan
authors: XY
authors: Wu
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000628:therapy; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051017:Apoptosis Regulatory Proteins / Q000032:analysis*; D000071186:Beclin-1; D014408:Biomarkers, Tumor / Q000032:analysis; D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology* / Q000628:therapy; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000032:analysis*; D008565:Membrane Proteins / Q000032:analysis*; D008875:Middle Aged; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D016019:Survival Analysis
chemical_list: D051017:Apoptosis Regulatory Proteins; D000071186:Beclin-1; D014408:Biomarkers, Tumor; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008565:Membrane Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; C491997:BECN1 protein, human; C497442:HIF1A protein, human; C508053:ERBB2 protein, human