Fibulin-1 functions as a prognostic factor in lung adenocarcinoma

Jpn J Clin Oncol. 2015 Sep;45(9):854-9. doi: 10.1093/jjco/hyv094. Epub 2015 Jul 16.

Abstract

Objective: Fibulin-1 is a member of the fibulin gene family, characterized by tandem arrays of epidermal growth factor-like domains and a C-terminal fibulin-type module. Fibulin-1 plays important roles in a range of cellular functions including morphology, growth, adhesion and mobility. It acts as a tumor suppressor gene in cutaneous melanoma, prostate cancer and gastric cancer. However, whether fibulin-1 also acts as a tumor suppressor gene in lung adenocarcinoma remains unknown. We also determined the association of fibulin-1 expression with various clinical and pathological parameters, which would show its potential role in clinical prognosis.

Methods: We investigated and followed up 140 lung adenocarcinoma patients who underwent lung resection without pre- and post-operative systemic chemotherapy at the Affiliated Hospital of Nantong University from 2009 to 2013. Western blot assay and immunohistochemistry were used to evaluate the expression of fibulin-1 in lung adenocarcinoma tissues. We then analyzed the correlations between fibulin-1 expression and clinicopathological variables as well as the patients' overall survival rate.

Results: Both western blot assay and immunohistochemistry demonstrated that the level of fibulin-1 was downregulated in human lung adenocarcinoma tissues compared with that of normal lung tissues. Fibulin-1 expression significantly correlated with histological differentiation (P = 0.046), clinical stage (P< 0.01), lymph node status (P = 0.038) and expression of Ki-67 (P = 0.013). More importantly, multivariate analysis revealed that fibulin-1 was an independent prognostic marker for lung adenocarcinoma, and high expression of fibulin-1 was significantly associated with better prognosis of lung adenocarcinoma patients.

Conclusions: The results supported our hypothesis that fibulin-1 can act as a prognostic factor in lung adenocarcinoma progression.

Keywords: fibulin-1; lung adenocarcinoma; prognosis; tumor suppressor gene.

MeSH terms

  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology*
  • Adenocarcinoma / surgery
  • Adenocarcinoma of Lung
  • Adult
  • Aged
  • Biomarkers, Tumor / metabolism
  • Blotting, Western
  • Calcium-Binding Proteins / metabolism*
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Ki-67 Antigen / metabolism
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology*
  • Lung Neoplasms / surgery
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Staging
  • Prognosis
  • Stomach Neoplasms / mortality

Substances

  • Biomarkers, Tumor
  • Calcium-Binding Proteins
  • Ki-67 Antigen
  • fibulin