Oncotarget

Research Papers:

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

Yongbing Chen, Menghua Du, Jin Wang, Pengfei Xing, Yongsheng Zhang, Feng Li and Xueguan Lu _

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Oncotarget. 2016; 7:48432-48442. https://doi.org/10.18632/oncotarget.10302

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Abstract

Yongbing Chen1, Menghua Du2, Jin Wang2, Pengfei Xing2, Yongsheng Zhang3, Feng Li3, Xueguan Lu2,4

1Department of Thoracic Surgery, the Second Affiliated Hospital of Soochow University, Suzhou, China

2Department of Oncology & Radiotherapy, the Second Affiliated Hospital of Soochow University, Suzhou, China

3Department of Pathology, the Second Affiliated Hospital of Soochow University, Suzhou, China

4Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China

Correspondence to:

Xueguan Lu, email: [email protected]

Keywords: lung cancer, stromal fibroblasts, miRNA-200a, hepatocyte growth factor, prognosis

Received: January 02, 2016     Accepted: June 06, 2016     Published: June 27, 2016

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.


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