Beclin 1 and p62 expression in non-small cell lung cancer: relation with malignant behaviors and clinical outcome

Int J Clin Exp Pathol. 2015 Sep 1;8(9):10644-52. eCollection 2015.

Abstract

Autophagy plays a complicated role in tumorigenesis in a variety of cancers. Recently, many studies report that some autophagy-related markers could be detected in several types of human tumors. However, fewer studies have been conducted to evaluate the relationship between autophagy and lung cancer, especially in non-small cell lung cancer (NSCLC). In this study, the expression levels of autophagy-related markers Beclin 1 and p62 were detected by Western blot analysis and cell immunofluorescence staining in three human NSCLC cell lines A549, H1299 and HCC827. Then, tissue microarray and immunohistochemical staining were used to determine Beclin 1 and p62 expression in 104 NSCLC specimens collected from patients. Beclin 1 and p62 were observed to primarily distribute in the cytoplasm of the cells. Beclin 1 was expressed more predominantly in male and heavy-smoker and its expression was significantly correlated with the differentiation and lymph node metastasis. p62 expression was negatively correlated with TNM stage and lymph node metastasis. Univariate Cox regression analysis revealed that low expression of Beclin 1 and high expression of p62 were significantly associated with shorter survival. Meanwhile, multivariate Cox regression analysis indicated that Beclin 1 and p62 were independent risk factors related to overall survival for patients with NSCLC. Collectively, our study suggests that Beclin 1 and p62 could serve as potential indicators for the prognosis of patients with NSCLC.

Keywords: Beclin 1; autophagy; non-small cell lung cancer; p62; prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / mortality
  • Adenocarcinoma / secondary
  • Adenocarcinoma / therapy
  • Adenocarcinoma of Lung
  • Apoptosis Regulatory Proteins / metabolism*
  • Autophagy
  • Beclin-1
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / secondary
  • Carcinoma, Non-Small-Cell Lung / therapy
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / secondary
  • Carcinoma, Squamous Cell / therapy
  • Cell Differentiation
  • Cell Line, Tumor
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • Lung Neoplasms / therapy
  • Lymphatic Metastasis
  • Male
  • Membrane Proteins / metabolism*
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Staging
  • Proportional Hazards Models
  • Risk Factors
  • Sequestosome-1 Protein
  • Smoking / adverse effects
  • Time Factors
  • Treatment Outcome

Substances

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