The prognostic value of osteopontin in limited-stage small cell lung cancer patients and its mechanism

Abstract

Osteopontin (OPN) is known to be overexpressed in numerous carcinomas. Although abundant OPN has been reported to be correlated with poor survival in non-small cell lung cancer (NSCLC) but their clinical and prognostic significance in SCLC remains unknown. In this study, RNA-sequencing was used to obtain gene expression data in SCLC tissue samples and OPN expression levels were then investigated using qPCR, immunohistochemical and Western blot. We found OPN was one of the most upregulated genes. Besides, the correlation of OPN with tumor clinicopathological characteristics was evaluated and we found OPN was associated with advanced tumor stages. In addition, Kaplan-Meier survival analysis and Cox analyses revealed OPN expression was an independent predictor for overall survival (OS) (P= 0.013) and progression-free survival (PFS) (P=0.008). A high level of OPN was correlated with pT classification and pN classification (P<0.05). Moreover, In vitro experiments, by test the biological function of OPN via colony formation, wound healing, Transwell assays, and western blotting, we found that overexpression of OPN induced cell proliferation, migration, and invasion; down-regulation of OPN inhibited these. Overexpression of OPN stimulates epithelial-mesenchymal transition (EMT) whereas OPN silencing prevents the EMT. In conclusion: OPN appears to contribute to the malignant mechanism of SCLC and is a promising and significant prognostic predictor in patients with SCLC. Specific silence of OPN could be a future direction to develop a novel therapeutic strategy for SCLC patients.