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

PLoS One. 2013 Nov 26;8(11):e80317. doi: 10.1371/journal.pone.0080317. eCollection 2013.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Apoptosis Regulatory Proteins / deficiency*
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / metabolism
  • Beclin-1
  • Cholangiocarcinoma / genetics*
  • Cholangiocarcinoma / mortality
  • Cholangiocarcinoma / pathology*
  • Cholangiocarcinoma / surgery
  • Female
  • Gene Expression
  • Humans
  • Immunohistochemistry
  • Lymph Nodes / pathology
  • Lymphatic Metastasis
  • Male
  • Membrane Proteins / deficiency*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • Tumor Burden

Substances

  • Apoptosis Regulatory Proteins
  • BECN1 protein, human
  • Beclin-1
  • Membrane Proteins

Grants and funding

This work was supported by National Natural Science Foundation of China (No. 81000934 & No. 81370060 to X.B. Wan, No. 81372566 to L. Wang, and No. 81372374 to X.Y. Wu); Natural Science Foundation of Guangdong Province (No. 10251008901000008 to L. Wang); Foundation for Distinguished Young Scholars of Sun Yat-sen University (No. 13ykzd20 to X.B. Wan); Foundation for Pearl River Science & Technology Young Scholars of Guangzhou (No. 2013030 to X.B. Wan); Science and Technology Foundation of Guangdong Province (2011B03180076 to Q. Lin); and Combination Project of Production, Education and Research from Ministry of Education & Guangdong Province (2012B091100460 to X.Y. Wu). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.