Prognostic Significance of LC3B and p62/SQSTM1 Expression in Gastric Adenocarcinoma

Anticancer Res. 2019 Dec;39(12):6711-6722. doi: 10.21873/anticanres.13886.

Abstract

Background/aim: Autophagy is a cellular mechanism that recycles cellular components to maintain homeostasis. To investigate the clinical implication of autophagy in gastric cancer, the autophagy markers with autophagosome formation, LC3B and selective autophagy substrate p62/SQSTM1 (P62) were validated.

Materials and methods: LC3B and p62 expression was examined using immunohistochemistry, western blot assays, and reverse-transcription polymerase chain reaction (RT-PCR). The relationship of LC3B and p62 expression in gastric adenocarcinomas with clinicopathological parameters, including patient survival, were analyzed.

Results: Normal gastric mucosae exhibit no LC3B and p62 expression, while tubular adenoma and gastric adenocarcinomas exhibit variable nuclear or cytoplasmic p62 expression. High LC3B, high cytoplasmic p62, and low nuclear p62 protein expression in gastric adenocarcinomas is positively correlated with poor prognostic factors including survival.

Conclusion: Dynamic LC3B and p62 changes are suggested to be involved in gastric tumorigenesis and cancer progression. LC3B and p62 could be used as prognostic biomarkers and potential therapeutic targets for gastric adenocarcinomas.

Keywords: Autophagy; LC3; SQSTM1; gastric cancer; p62; prognosis.

MeSH terms

  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology
  • Adenoma / metabolism*
  • Adenoma / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Autophagic Cell Death / physiology*
  • Biomarkers, Tumor / metabolism*
  • Cell Nucleus / metabolism
  • Cytoplasm / metabolism
  • Female
  • Gastric Mucosa / metabolism
  • Humans
  • Male
  • Microtubule-Associated Proteins / metabolism*
  • Middle Aged
  • Prognosis
  • Sequestosome-1 Protein / metabolism*
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / mortality
  • Stomach Neoplasms / pathology
  • Young Adult

Substances

  • Biomarkers, Tumor
  • MAP1LC3B protein, human
  • Microtubule-Associated Proteins
  • SQSTM1 protein, human
  • Sequestosome-1 Protein