Decreased expression of LKB1 is associated with epithelial-mesenchymal transition and led to an unfavorable prognosis in gastric cancer

Hum Pathol. 2019 Jan:83:133-139. doi: 10.1016/j.humpath.2018.08.017. Epub 2018 Aug 30.

Abstract

Liver kinase B1 (LKB1) is a newly discovered tumor suppressor gene that plays a role in tumorigenesis and cancer progression. However, LKB1 expression and its precise impact on gastric cancer (GC) have not yet been elucidated. The aim of this study was to explore the significance of LKB1 expression, as well as its correlation with epithelial-mesenchymal transition (EMT) in GC. In the present study, LKB1 protein was detected in 107 GC tissue samples and adjacent paracancerous tissues by immunohistochemical staining. The relationship of LKB1 expression with clinicopathological features and its correlation with 3 EMT-related markers (E-cadherin, β-catenin, and vimentin) in GC were analyzed. Results revealed that the expression of LKB1 was decreased in GC tissues compared with that in adjacent paracancerous tissues (P = .005). GC patients with greater invasion depth (P = .007), higher pathological TNM stage (P = .014), and lymph node metastasis (P = .026) showed lower LKB1 expression; furthermore, E-cadherin and β-catenin expression decreased, whereas vimentin expression increased (all P < .05). Kaplan-Meier analysis indicated that the expression of LKB1, E-cadherin, β-catenin, and vimentin, as well as differentiation, invasion, pathological TNM, and lymph node metastasis, was associated with disease-free survival (DFS) (all P < .05). Multivariate analysis also showed that LKB1 expression (hazard ratio, 0.578 [0.351-0.950]; P = .031) may be an independent factor for DFS. In conclusion, LKB1 expression was decreased in GC, and this positively correlated with EMT and a shorter DFS, suggesting that LKB1 could act as an independent factor in predicting GC progression.

Keywords: Disease-free survival; Epithelial-mesenchymal transition; Gastric cancer; LKB1; Prognosis.

MeSH terms

  • AMP-Activated Protein Kinase Kinases
  • Adult
  • Aged
  • Biomarkers, Tumor / analysis*
  • Disease-Free Survival
  • Epithelial-Mesenchymal Transition / physiology*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Prognosis
  • Protein Serine-Threonine Kinases / analysis
  • Protein Serine-Threonine Kinases / biosynthesis*
  • Retrospective Studies
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / mortality
  • Stomach Neoplasms / pathology*

Substances

  • Biomarkers, Tumor
  • Protein Serine-Threonine Kinases
  • STK11 protein, human
  • AMP-Activated Protein Kinase Kinases