MiRNA-200a expression is inverse correlation with hepatocyte growth factor expression in stromal fibroblasts and its high expression predicts a good prognosis in patients with non-small cell lung cancer

Abstract

Cancer-associated fibroblasts (CAFs) play an important role in favoring tumor progression. However, little is known concerning expression of miRNA-200a and its potential target gene hepatocyte growth factor (HGF) in CAFs. In the present study, we investigated expression levels and prognostic significance of miRNA-200a and HGF in stromal fibroblasts of non-small cell lung cancer (NSCLC), and evaluated the correlation between miRNA-200a and HGF. In situ hybridization and immunohistochemical staining were used to investigate expression levels of miRNA-200a and HGF in 134 formalin-fixed paraffin-embedded tumor specimens from clinical stage I -IIIA NSCLC, respectively. The results showed a significant inverse correlation existed between miRNA-200a and HGF expression level in stromal fibroblasts (χ² = 21.778, p = 0.000). In vitro, the upregulation of miRNA-200a reduced expression of HGF protein in human CAFs. The 3-year overall survival (OS) rates with low and high miRNA-200a expression in stromal fibroblasts were 39.0% and 53.4%, respectively (χ²=4.25, p=0.039). The 3-year OS rates with low and high HGF expression in stromal fibroblasts were 60.3% and 31.8%, respectively (χ²=12.55, p=0.000). The multivariate analysis showed that clinical stage and HGF expression level in stromal fibroblasts were the independent predictive factors of OS. These results suggested that miRNA-200a expression was inverse correlation with HGF expression in stromal fibroblasts. High miRNA-200a and low HGF expression in stromal fibroblasts may predict a good prognosis in patients with NSCLC.