Beclin 1 deficiency correlated with lymph node metastasis, predicts a distinct outcome in intrahepatic and extrahepatic cholangiocarcinoma

• Published in: PloS one Vol. 8; no. 11; p. e80317
• Main Authors: Wang, Tian-Tian, Cao, Qing-Hua, Chen, Ming-Yuan, Xia, Qing, Fan, Xin-Juan, Ma, Xiao-Kun, Lin, Qu, Jia, Chang-Chang, Dong, Min, Ruan, Dan-Yun, Lin, Ze-Xiao, Wen, Jing-Yun, Wei, Li, Li, Xing, Chen, Zhan-Hong, Wang, Lei, Wu, Xiang-Yuan, Wan, Xiang-Bo
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 26.11.2013; Public Library of Science (PLoS)
• Subjects: Adult; Aged; Apoptosis; Apoptosis Regulatory Proteins - deficiency; Apoptosis Regulatory Proteins - genetics; Apoptosis Regulatory Proteins - metabolism; Autophagy; Beclin-1; Bioindicators; Biomarkers; Cell death; Chemotherapy; Cholangiocarcinoma; Cholangiocarcinoma - genetics; Cholangiocarcinoma - mortality; Cholangiocarcinoma - pathology; Cholangiocarcinoma - surgery; Cirrhosis; Correlation analysis; Female; Gene Expression; Hepatology; Humans; Hypoxia; Immunohistochemistry; Kinases; Laboratories; Liver; Liver cancer; Liver cirrhosis; Lymph; Lymph nodes; Lymph Nodes - pathology; Lymphatic Metastasis; Lymphatic system; Male; Medical prognosis; Membrane Proteins - deficiency; Membrane Proteins - genetics; Membrane Proteins - metabolism; Metastases; Metastasis; Middle Aged; Multivariate analysis; Neoplasm Staging; Oncology; Patients; Phagocytosis; Prognosis; Radiation therapy; Surgery; Survival; Tumor Burden; Tumorigenesis; Tumors; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0080317

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.