The predictive value and potential mechanisms of miRNA-328 and miRNA-378 for brain metastases in operable and advanced non-small-cell lung cancer

Jpn J Clin Oncol. 2015 May;45(5):464-73. doi: 10.1093/jjco/hyv009. Epub 2015 Feb 2.

Abstract

Objective: The incidence of brain metastases greatly varies in patients with non-small-cell lung cancer, and molecular markers are considered to predict brain metastases. Therefore, this study sought to identify the predictive value and potential mechanisms of miRNA-328 and miRNA-378 for brain metastases in non-small-cell lung cancer.

Methods: Patients who received a curable surgery for their lung cancer were screened according to our criteria. Formalin-fixed paraffin-embedded samples from the patients were examined for the expression of miRNA-328 and miRNA-378 using real-time polymerase chain reaction and the expression of N-cadherin, E-cadherin, vascular endothelial growth factor, protein kinase Cα and S100B were investigated using immunohistochemical staining.

Results: In total, 86 patients were screened for this study and 23 patients were diagnosed with brain metastases during the follow-up period. Comparing patients with and without brain metastases, the expression of miRNA-328 and miRNA-378 in tumor tissues were significantly different (P = 6.2 × 10(-5) and P = 2.8 × 10(-5), respectively). For the patients with brain metastases, the expression of miRNA-328 and miRNA-378 in tumor tissues compared with para-carcinoma tissues were also significantly different (P = 2.2 × 10(-5) and P = 1.6 × 10(-5), respectively). For patients with brain metastases, the association between miRNA-328 and protein kinase Cα was significant (r = 0.591, P = 0.003), but that between miRNA-378 and protein kinase Cα was not significant (r = 0.259, P = 0.232).

Conclusions: The expression of miRNA-328 and miRNA-378 in tumor tissues can be used to predict brain metastases in patients with non-small-cell lung cancer. miRNA-328 might promote brain metastases by regulating the expression of protein kinase Cα. However, the mechanisms of miRNA-378 to promote brain metastases should be studied in the future.

Keywords: brain metastases; miRNA-328; miRNA-378; non-small-cell lung cancer; predictive value.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers, Tumor / analysis*
  • Biomarkers, Tumor / blood
  • Brain Neoplasms / enzymology
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / secondary*
  • Cadherins / analysis
  • Carcinoma, Non-Small-Cell Lung / chemistry
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / secondary*
  • Carcinoma, Non-Small-Cell Lung / surgery
  • Female
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • Lung Neoplasms / chemistry
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology*
  • Lung Neoplasms / surgery
  • Male
  • MicroRNAs / analysis*
  • MicroRNAs / blood
  • Middle Aged
  • Predictive Value of Tests
  • Protein Kinase C-alpha / analysis*
  • Real-Time Polymerase Chain Reaction
  • S100 Calcium Binding Protein beta Subunit / analysis
  • Tissue Culture Techniques
  • Vascular Endothelial Growth Factor A / analysis

Substances

  • Biomarkers, Tumor
  • Cadherins
  • MicroRNAs
  • S100 Calcium Binding Protein beta Subunit
  • S100B protein, human
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Protein Kinase C-alpha