Prognostic significance of Beclin 1 in intrahepatic cholangiocellular carcinoma

• Published in: Autophagy 2011-10, Vol.7 (10), p.1222-1229
• Main Authors: Dong, Li-Wei, Hou, Yu-Jie Hou, Tan, Ye-Xiong, Tang, Liang, Pan, Yu-Fei, Wang, Min, Wang, Hong-Yang
• Format: Article
• Language: English
• Subjects: Aged; Apoptosis Regulatory Proteins - metabolism; Autophagy; Beclin-1; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Binding; Biology; Bioscience; Calcium; Cancer; Cell; Cholangiocarcinoma - diagnosis; Cholangiocarcinoma - metabolism; Cycle; Disease Progression; Female; Gene Expression Regulation, Neoplastic; Humans; Landes; Liver Neoplasms - diagnosis; Liver Neoplasms - metabolism; Lymphatic Metastasis; Male; Membrane Proteins - metabolism; Middle Aged; Neoplasm Metastasis; Organogenesis; Prognosis; Proteins; RNA, Messenger - metabolism
• ISSN: 1554-8627; 1554-8635
• DOI: 10.4161/auto.7.10.16610

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.