Decreased expression of Beclin 1 correlates with a metastatic phenotypic feature and adverse prognosis of gastric carcinomas

J Surg Oncol. 2012 May;105(6):542-7. doi: 10.1002/jso.22151. Epub 2011 Nov 17.

Abstract

Background and objectives: Beclin 1 plays a critical role in the regulation of autophagy, apoptosis, differentiation and the development and progression of cancer. The clinicopathological significance of Beclin 1 expression in patients with gastric carcinoma (GC) has not been yet elucidated.

Methods: Immunohistochemistry (IHC) was performed to investigate the Beclin 1 expression in GCs and normal mucosal tissues. Receiver operating characteristic curve analysis, spearman's rank correlation, Kaplan-Meier plots and Cox proportional hazards regression model were used to analyze the data.

Results: The highly expressed Beclin 1 was observed in 90/155 (58.1%) of GCs, in 24/60 (40.0%) adjacent mucosal tissues and in 13/30 (43.3%) of normal gastric mucosa tissues (P = 0.036). Decreased expression of Beclin 1 in cancer cells was significantly correlated with poor differentiation, nodal and distant metastasis, advanced TNM stage, and tumor relapse. More importantly, Decreased expression of Beclin 1 was associated with shorter survival as evidenced by univariate and multivariate analysis.

Conclusions: Our findings provide a basis for the concept that decreased expression of Beclin 1 in GC may be important in the acquisition of a metastatic phenotype, suggesting that decreased Beclin 1 expression, as examined by IHC, is an independent biomarker for poor prognosis of patients with GC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Apoptosis Regulatory Proteins / metabolism*
  • Beclin-1
  • Carcinoma / metabolism
  • Carcinoma / mortality
  • Carcinoma / pathology
  • Case-Control Studies
  • Gastric Mucosa / metabolism
  • Genes, Tumor Suppressor
  • Humans
  • Immunohistochemistry
  • Lymphatic Metastasis
  • Membrane Proteins / metabolism*
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Metastasis
  • Neoplasm Recurrence, Local
  • Prognosis
  • Proportional Hazards Models
  • ROC Curve
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / mortality*
  • Stomach Neoplasms / pathology
  • Young Adult

Substances

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