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Beclin 1 Deficiency Correlated with Lymph Node Metastasis,Predicts a Distinct Outcome in Intrahepatic and Extrahepatic Cholangiocarcinoma
Authors:Tian-Tian Wang  Qing-Hua Cao  Ming-Yuan Chen  Qing Xia  Xin-Juan Fan  Xiao-Kun Ma  Qu Lin  Chang-Chang Jia  Min Dong  Dan-Yun Ruan  Ze-Xiao Lin  Jing-Yun Wen  Li Wei  Xing Li  Zhan-Hong Chen  Lei Wang  Xiang-Yuan Wu  Xiang-Bo Wan
Abstract:Autophagy can be tumor suppressive as well as promotive in regulation of tumorigenesis and disease progression. Accordingly, the prognostic significance of autophagy key regulator Beclin 1 was varied among different tumors. Here, we detected the clinicopathological and prognostic effect of Beclin 1 in the subtypes of intrahepatic cholangiocarcinoma (ICC) and extrahepatic cholangiocarcinoma (ECC). Beclin 1 expression level was detected by immunohistochemistry staining in 106 ICC and 74 ECC patients. We found that Beclin 1 was lowly expressed in 126 (70%) cholangiocarcinoma patients, consist of 72 ICC and 54 ECC. Moreover, the cholangiocarcinoma patients with lymph node metastasis (N1) had a lower Beclin 1 level than that of N0 subgroup (P=0.012). However, we did not detect any correlations between Beclin 1 and other clinicopathological features, including tumor subtypes, vascular invasion, HBV infection, liver cirrhosis, cholecystolithiasis and TNM stage. Survival analysis showed that, compared with the high expression subset, Beclin 1 low expression was correlated with a poorer 3-year progression-free survival (PFS, 69.1% VS 46.8%, P=041) for cholangiocarcinoma. Importantly, our stratified univariate and multivariate analysis confirmed that Beclin 1 lowly expressed ICC had an inferior PFS as well as overall survival than ECC, particularly than that of Beclin 1 highly expressed ECC patients. Thus, our study demonstrated that Beclin 1low expression, correlated with lymph node metastasis, and might be a negative prognostic biomarker for cholangiocarcinoma. Combined Beclin 1 level with the anatomical location might lead to refined prognosis for the subtypes of ICC and ECC.
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