Decreased expression of Beclin 1 correlates closely with Bcl-xL expression and poor prognosis of ovarian carcinoma

PLoS One. 2013;8(4):e60516. doi: 10.1371/journal.pone.0060516. Epub 2013 Apr 3.

Abstract

Background: It has been suggested that autophagy-related Beclin 1 plays a critical role in the regulation of tumor development and/or progression, but its prognostic significance and relationship with Bcl-xL expression in ovarian carcinoma are unclear.

Methodology/principal findings: In the present study, the methods of Western blotting and immunohistochemistry (IHC) were utilized to investigate the expression status of Beclin 1 and Bcl-xL in fresh ovarian tissues and paraffin-embedded epithelial ovarian tumor tissues. Decreased expression of Beclin 1 was examined by IHC in 8.3% of normal ovaries, in 15.4% of cystadenomas, in 20.0% of borderline tumors, and in 55.6% of ovarian carcinomas, respectively. In ovarian carcinomas, decreased expression of Beclin 1 was correlated closely with ascending histological grade, later pT/pN/pM status and/or advanced clinical stage (P<0.05). In univariate survival analysis, a highly significant association between low-expressed Beclin 1 and shortened patient survival was evaluated in ovarian carcinoma patients (P<0.01), and Beclin 1 expression was an independent prognostic factor as evidenced by multivariate analysis (P = 0.013). In addition, decreased expression of Beclin 1 was inversely correlated with altered expression of Bcl-xL in ovarian carcinoma cohort, and combined analysis further showed that the low Beclin 1/high Bcl-xL group had the lowest survival rate.

Conclusions/significance: Our findings suggest that Beclin 1 expression, as examined by IHC, could be served as an additional tool in identifying ovarian carcinoma patients at risk of tumor progression, and predicting patient survival in ovarian carcinomas with increased expression of Bcl-xL.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Apoptosis Regulatory Proteins / metabolism*
  • Area Under Curve
  • Beclin-1
  • Carcinoma / metabolism*
  • Carcinoma / mortality
  • Cystadenoma / metabolism*
  • Cystadenoma / mortality
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Membrane Proteins / metabolism*
  • Middle Aged
  • Multivariate Analysis
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / mortality
  • Prognosis
  • Proportional Hazards Models
  • ROC Curve
  • Tissue Array Analysis
  • bcl-X Protein / metabolism*

Substances

  • Apoptosis Regulatory Proteins
  • BCL2L1 protein, human
  • BECN1 protein, human
  • Beclin-1
  • Membrane Proteins
  • bcl-X Protein

Grants and funding

This study was supported by grants from the National Nature Science Foundation of China (No. 81225018), the Ph.D. Programs Foundation of Ministry of Education of China (No. 20110171110078), and the 973 Project of China (2010CB529401). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.