Autophagy 2011 Oct;7 (10): 1222-9. [IF:6.643]
Prognostic significance of Beclin 1 in intrahepatic cholangiocellular carcinoma.
Dong LW , Hou YJ , Tan YX , Tang L , Pan YF , Wang M , Wang HY .
International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, the Second Military Medical University, Shanghai, China.
上海第二军医大学，国际合作信号转导实验室，东方肝胆外科研究所
Abstract
Autophagy enables cells to recycle long-lived proteins or damaged organelles. Beclin 1 plays important roles in autophagy, differentiation, apoptosis and the development and progression of cancer, but the expression of Beclin 1 and its possible role in primary intrahepatic cholangiocarcinoma (ICC) has not been reported yet. This study aimed to investigate Beclin 1 expression and its prognostic significance in ICC. First, we assessed the expression levels of Becn1 by real-time PCR in 50 ICC samples and found Becn1 mRNA expression was markedly increased in 78% (39 of 50) samples compared with normal bile duct epithelium. Beclin 1 protein expression in 108 tumor specimens from patients diagnosed with ICC was examined by immunohistochemistry and the correlation between Beclin 1 expression and clinicopathological factors were investigated. Immunopositivity for Beclin 1 was found in 72.2% (78 of 108) samples and low Beclin 1 expression was significantly associated with lymph node metastasis. The correlation between Beclin 1 expression and metastasis was validated in 46 ICC samples with lymph node metastasis. In survival analysis, low Beclin 1 expression was associated with worse overall survival (OS; p = 0.025) and disease-free survival (DFS; p = 0.027). In multivariate analysis, Beclin 1 expression, intrahepatic metastasis, lymph node metastasis and tumor size were found to be independent prognostic factors of OS. Thus, our results suggested the expression of Beclin 1 was correlated with progression and metastasis of ICC and it might serve as a novel prognostic marker for patients with ICC.
摘要
自噬作用使细胞内长寿命的蛋白质或受损的细胞器的再循环成为可能。Beclin1在自噬、分化、凋亡和肿瘤的发生和进展当中起重要作用。但是Beclin1的表达以及它在原发型的肝内胆管细胞癌中的作用还没有被报道。该研究的目的是研究Beclin1的表达以及它在肝内胆管细胞癌中的预后意义。首先我们对50个肝内胆管细胞癌样本进行实时定量PCR以评估Becn1的基因表达水平，结果提示和正常的胆管上皮比较，肝内胆管细胞癌的Becn1mRNA表达水平显著提高的占78%(39 of 50)。从108位被诊断为肝内胆管细胞癌的患者中获取的肿瘤标本进行免疫组化以检测Beclin1蛋白的表达情况。同时，进行了Beclin1蛋白的表达情况和临床病理因素的相关性分析。其中，Beclin1免疫阳性的占72.2%(78 of 108)，通过46名淋巴结转移样本分析，Beclin1的低表达和淋巴结转移有显著地相关性。在生存性分析中，Beclin1的低表达和较低总生存期和无病生存期相关。在多变量分析中，Beclin1的表达，肝内转移，淋巴结转移和肿瘤的大小被认为是总生存期的独立预后因素。因此，我们的结果表明Beclin1的表达肝内胆管细胞癌的预后和转移密切相关，它可能作为肝内胆管细胞癌患者的一个新的预后指标。
