Document Detail


Elevated Beclin 1 expression is correlated with HIF-1alpha in predicting poor prognosis of nasopharyngeal carcinoma.
MedLine Citation:
PMID:  20150769     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Recent studies have suggested that autophagy plays a pivotal role in regulation of cancer development and progression. High expression of the autophagy-related Beclin 1 protein predicted favorable patient outcome in several tumors. Here, a randomized controlled trial (RCT)-derived 128 nasopharyngeal carcinoma (NPC) patients were subjected to analysis of Beclin 1 expression and survival probability. In this RCT, 61 patients treated with induction chemotherapy plus concurrent chemoradiotherapy were used as a training set to generate a Beclin 1 cutoff score for patient outcome by receiver operating characteristic (ROC) curve analysis. For validation, the ROC-derived cutoff point was subjected to analysis of the association of Beclin 1 expression with patient outcome and clinical characteristics in testing set. The testing set comprised of 67 patients received induction chemotherapy plus radiotherapy. In the testing set and overall patients, our univariate and multivariate analysis showed that higher Beclin 1 expression, defined by the training set ROC analysis-generated cutoff score, predicted poorer overall survival, progression-free survival and distant metastasis-free survival. However, we failed to detect a correlation between Beclin 1 and local failure-free survival. Moreover, a positive relationship between Beclin 1 and HI F-1alpha expression was found. Importantly, among patients with elevated HI F-1alpha expression, a subset with lower Beclin 1 expression displayed a significant overall survival advantage than those with higher expression (p = 0.036). Contrary to previous studies, our results demonstrated that high autophagic Beclin 1 expression was an inferior prognostic marker for NPC. HI F-1alpha-associated Beclin 1 high expression might facilitate NPC cells surviving from chemoradiotherapy, suggesting a novel therapeutic molecular target for NPC.
Authors:
Xiang-Bo Wan; Xin-Juan Fan; Ming-Yuan Chen; Jin Xiang; Pei-Yu Huang; Ling Guo; Xiang-Yuan Wu; Jie Xu; Zi-Jie Long; Yan Zhao; Wei-Hua Zhou; Hai-Qiang Mai; Quentin Liu; Ming-Huang Hong
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Publication Detail:
Type:  Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't     Date:  2010-04-26
Journal Detail:
Title:  Autophagy     Volume:  6     ISSN:  1554-8635     ISO Abbreviation:  Autophagy     Publication Date:  2010 Apr 
Date Detail:
Created Date:  2010-04-23     Completed Date:  2010-08-12     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101265188     Medline TA:  Autophagy     Country:  United States    
Other Details:
Languages:  eng     Pagination:  395-404     Citation Subset:  IM    
Affiliation:
State Key Laboratory of Oncology in Southern China, Cancer Center, Sun Yat-sen University, Guangzhou, China.
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Aged
Antineoplastic Agents / therapeutic use
Apoptosis Regulatory Proteins / metabolism*
Combined Modality Therapy
Female
Humans
Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
Kaplan-Meiers Estimate
Male
Membrane Proteins / metabolism*
Nasopharyngeal Neoplasms / diagnosis*,  drug therapy,  metabolism*,  radiotherapy
Prognosis
Proportional Hazards Models
ROC Curve
Treatment Outcome
Young Adult
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Apoptosis Regulatory Proteins; 0/BECN1 protein, human; 0/Hypoxia-Inducible Factor 1, alpha Subunit; 0/Membrane Proteins

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