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.

Prognostic Role of MicroRNAs in Human Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis

“…Twenty-eight studies reported on tumors at various stages of clinical presentation, whereas this information was absent in seven studies [ 13 – 15 , 20 , 21 ]. In situ hybridization (ISH) was utilized in four studies [ 15 , 22 , 23 ], while miRNA array and quantitative real-time PCR (qRT-PCR) remained the predominant techniques for miRNA detection in the remaining studies.…”

“…Some miRNAs that were chosen empirically or without clear justification in studies could have led to imprecise outcomes. The number of statistically insignificant studies [ 16 , 20 , 23 , 24 ] was 15.6% (5 out of 32) and may have limited the statistical power. Patient age could be another variable that might have contributed towards heterogeneity, as four out of the 32 studies [ 16 , 22 , 50 , 51 ] showed significant association of age with OS in NSCLC patients.…”

miRNAtools: Advanced Training Using the miRNA Web of Knowledge

“…This tutorial describes how gene expression data can be used to characterize the putative action of a group of miRNAs via correlation analysis. In a biological system, an inverse correlation of expression levels between a miRNA and its cognate target is expected, but whether this effect is evident at the level of mRNA transcript depends on the specific characteristics of the considered mRNA [ 31 , 32 ]. In this tutorial, we describe the use of a web-based tool named MirTarVis+ [ 14 , 33 ], which is able to perform such a correlation analysis, with results depicted in a graphical manner.…”

A review of microRNAs related to the occurrence, diagnosis, and prognosis of non-small cell lung cancer

“…The expression of miR-200 A in matrix fibroblasts is negatively correlated with HGF expression. High miR-200a and low HGF expression in stromal fibroblasts may predict a good prognosis in patients with NSCLC [52] . Further, Zhao and his colleagues [53] .…”