Low expression of MAP1LC3B, associated with low Beclin-1, predicts lymph node metastasis and poor prognosis of gastric cancer

Tumour Biol. 2016 Nov;37(11):15007-15017. doi: 10.1007/s13277-016-5383-5. Epub 2016 Sep 22.

Abstract

Since the roles of autophagy in gastric cancer remain unclear, we aim to investigate the expression of autophagy-related proteins MAP1LC3B and Beclin-1 in human gastric cancer and discuss their clinical significance and correlation with prognosis of patients with gastric cancer. A total of 160 consecutive patients with gastric cancer who had undergone gastrectomy were enrolled in this study. The expressions of MAP1LC3B and Beclin-1 were assessed by immunohistochemistry. The protein expression rates were analyzed with χ 2 and Fisher's exact tests. Survival analysis (overall survival (OS) and relapse-free survival (RFS)) was determined using the Kaplan-Meier method and Cox's proportional hazard regression model. Both the expressions of MAP1LC3B and Beclin-1 were lower in gastric cancer tissues than adjacent normal tissues (57 vs. 82 %, p = 0.007; 72 vs. 88 %, p = 0.046, respectively). Relativity analysis indicated MAP1LC3B expression was positively correlated with Beclin-1 expression (r = 0.424, p < 0.001). Both the MAP1LC3B-high-expression patients and Beclin-1-high-expression patients have longer OS time and RFS time than MAP1LC3B-low-expression patients and Beclin-1-low-expression patients (MAP1LC3B: both p < 0.001; Beclin-1: p = 0.014, p = 0.015, respectively). High simultaneous MAP1LC3B and Beclin-1 expressions were associated with longer OS and RFS compared with low simultaneous MAP1LC3B and Beclin-1 expressions (56.77 vs. 24.42 months, p < 0.001; 53.56 vs. 22.33 months, p < 0.001, respectively). Multivariate survival analysis showed both MAP1LC3B and Beclin-1 were independent prognostic factors for OS time (p = 0.016, p = 0.041, respectively). However, MAP1LC3B (p = 0.022) was an independent prognostic factor for RFS. Moreover, low expressions of MAP1LC3B and Beclin-1 were significantly associated with lymph node metastasis (p = 0.007, p = 0.030, respectively). The loss of MAP1LC3B, correlated with loss of Beclin-1, was observed in gastric cancer and correlated with poor prognosis and lymph node metastasis of gastric cancer patients.

Keywords: Beclin-1; Gastric cancer; Lymph node metastasis; MAP1LC3B; Prognosis.

MeSH terms

  • Adenocarcinoma / metabolism
  • Adenocarcinoma / secondary*
  • Adenocarcinoma / surgery
  • Adult
  • Aged
  • Aged, 80 and over
  • Beclin-1 / metabolism*
  • Biomarkers, Tumor / metabolism*
  • Female
  • Follow-Up Studies
  • Gastrectomy
  • Humans
  • Immunoenzyme Techniques
  • Lymphatic Metastasis
  • Male
  • Microtubule-Associated Proteins / metabolism*
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Prognosis
  • ROC Curve
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology*
  • Stomach Neoplasms / surgery
  • Survival Rate

Substances

  • BECN1 protein, human
  • Beclin-1
  • Biomarkers, Tumor
  • MAP1LC3B protein, human
  • Microtubule-Associated Proteins