Clinicopathological Correlations of Autophagy-related Proteins LC3, Beclin 1 and p62 in Gastric Cancer

Anticancer Res. 2016 Jan;36(1):129-36.

Abstract

Aim: This study evaluated the clinicopathological significance of autophagy, an intracellular degradation system, in gastric cancer.

Materials and methods: The expression levels of three autophagy-related proteins, namely light chain 3 (LC3), Beclin 1 and p62, were analyzed by immunohistochemistry using samples from 510 patients with primary gastric cancer.

Results: LC3, Beclin 1, and p62 expression was positive in 79 (15.5%), 126 (24.7%) and 251 (49.2%) out of 510 carcinomas, respectively. Autophagy was defined when samples were positive for at least two out of the three proteins. Autophagy-positive cases were 113 (22.1%) out of the 510. Autophagy determined by LC3, Beclin 1, and p62 significantly correlated with lymph node metastasis, vessel invasion, and hepatic metastasis. A Kaplan-Meier survival curve showed that autophagy was significantly associated with poor survival of patients with gastric cancer, especially for those with disease at stage I. Multivariate analysis indicated that autophagy was an independent prognostic factor.

Conclusion: Autophagy promotes the progression of gastric cancer at an early clinical stage.

Keywords: Beclin 1; Gastric cancer; LC3; autophagy; p62.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / analysis*
  • Adult
  • Aged
  • Aged, 80 and over
  • Apoptosis Regulatory Proteins / analysis*
  • Autophagy*
  • Beclin-1
  • Biomarkers, Tumor / analysis*
  • Chi-Square Distribution
  • Female
  • Gastrectomy
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Liver Neoplasms / secondary
  • Lymphatic Metastasis
  • Male
  • Membrane Proteins / analysis*
  • Microtubule-Associated Proteins / analysis*
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Proportional Hazards Models
  • Risk Factors
  • Sequestosome-1 Protein
  • Stomach Neoplasms / chemistry*
  • Stomach Neoplasms / mortality
  • Stomach Neoplasms / pathology
  • Stomach Neoplasms / surgery
  • Time Factors
  • Treatment Outcome
  • Young Adult

Substances

  • Adaptor Proteins, Signal Transducing
  • Apoptosis Regulatory Proteins
  • BECN1 protein, human
  • Beclin-1
  • Biomarkers, Tumor
  • MAP1LC3A protein, human
  • Membrane Proteins
  • Microtubule-Associated Proteins
  • SQSTM1 protein, human
  • Sequestosome-1 Protein