Liu Fanglei, Bai Chunxue, Guo Zhongliang
Department of Respiratory Medicine, Zhongshan Hospital Affiliated to Fudan University, Shanghai, China.
Department of Respiratory Medicine, Dongfang Hospital Affiliated to Tongji University, Shanghai, China.
Oncotarget. 2017 Jul 26;8(41):70084-70096. doi: 10.18632/oncotarget.19589. eCollection 2017 Sep 19.
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, 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.
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.
已知骨桥蛋白(OPN)在多种癌症中过度表达。尽管已有报道称非小细胞肺癌(NSCLC)中大量的OPN与较差的生存率相关,但其在小细胞肺癌(SCLC)中的临床和预后意义仍不清楚。在本研究中,使用RNA测序获取SCLC组织样本中的基因表达数据,然后使用qPCR、免疫组织化学和蛋白质印迹法研究OPN表达水平。我们发现OPN是上调最明显的基因之一。此外,评估了OPN与肿瘤临床病理特征的相关性,发现OPN与晚期肿瘤分期相关。此外,Kaplan-Meier生存分析和Cox分析显示,OPN表达是总生存期(OS)(P=0.013)和无进展生存期(PFS)(P=0.008)的独立预测指标。高水平的OPN与pT分类和pN分类相关(P<0.05)。此外,通过集落形成、伤口愈合、Transwell实验和蛋白质印迹法检测OPN的生物学功能,我们发现OPN的过表达诱导细胞增殖、迁移和侵袭;OPN的下调则抑制这些作用。OPN的过表达刺激上皮-间质转化(EMT),而OPN的沉默则阻止EMT。
OPN似乎参与了SCLC的恶性机制,是SCLC患者有前景且重要的预后预测指标。OPN的特异性沉默可能是为SCLC患者开发新治疗策略的未来方向。