Prognostic significance of Beclin 1 in intrahepatic cholangiocellular carcinoma
Prognostic significance of Beclin 1 in intrahepatic cholangiocellular carcinoma
复制标题
Beclin 1 在肝内胆管细胞癌中的预后意义
DOI：
10.4161/auto.7.10.16610
复制
发表时间：
2011-10-01
期刊：
影响因子：
13.3
通讯作者：
Wang, Hong-Yang
中科院分区：
文献类型：
--
作者：
Dong, Li-Wei;Hou, Yu-Jie;Wang, Hong-Yang
自噬使细胞能够回收长寿命的蛋白质或受损的细胞器。Beclin 1在自噬、分化、凋亡及肿瘤的发生发展中起重要作用，但Beclin 1在原发性肝内胆管细胞癌（ICC）中的表达及其可能的作用尚未见报道。本研究旨在探讨Beclin 1在ICC中的表达及其预后意义。首先，我们通过实时PCR评估了50例ICC样本中Becn 1的表达水平，发现与正常胆管上皮相比，78%（39/50）的样本中Becn 1 mRNA表达显著增加。采用免疫组化法检测108例ICC患者肿瘤组织中Beclin 1蛋白的表达，并分析其与临床病理因素的关系。72.2%（78/108）的样本中发现Beclin 1的免疫阳性，Beclin 1的低表达与淋巴结转移显著相关。在46例有淋巴结转移的ICC中验证了Beclin 1表达与转移的相关性。在生存分析中，低Beclin 1表达与较差的总生存期（OS; p = 0.025）和无病生存期（DFS; p = 0.027）相关。多因素分析发现Beclin 1表达、肝内转移、淋巴结转移和肿瘤大小是影响OS预后的独立因素，提示Beclin 1表达与ICC的进展和转移有关，可作为判断ICC预后的新指标。
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.