Elevated Beclin 1 expression is correlated with HIF-1alpha in predicting poor prognosis of nasopharyngeal carcinoma.
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.
Wan
Xiang-Bo
XB
State Key Laboratory of Oncology in Southern China, Cancer Center, Sun Yat-sen University, Guangzhou, China.
Fan
Xin-Juan
XJ
Chen
Ming-Yuan
MY
Xiang
Jin
J
Huang
Pei-Yu
PY
Guo
Ling
L
Wu
Xiang-Yuan
XY
Xu
Jie
J
Long
Zi-Jie
ZJ
Zhao
Yan
Y
Zhou
Wei-Hua
WH
Mai
Hai-Qiang
HQ
Liu
Quentin
Q
Hong
Ming-Huang
MH
D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D000071186:Beclin-1; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D053208:Kaplan-Meier Estimate; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D009303:Nasopharyngeal Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000378:metabolism* / Q000532:radiotherapy; D011379:Prognosis; D016016:Proportional Hazards Models; D012372:ROC Curve; D016896:Treatment Outcome; D055815:Young Adult
D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008565:Membrane Proteins