Nestin servers as a promising prognostic biomarker in non-small cell lung cancer

Lung cancer is currently the leading cause of cancer-related death worldwide and it is important to identify the predictive and/or prognostic markers for the cancer. Nestin, a proliferative and multipotent biomarker has been reported to be associated with prognosis in non-small cell lung cancer (NSCLC) in a few studies. In the present study, we retrospectively recruited 153 patients with NSCLC. Nestin protein expression in tumor samples was determined by immunohistochemistry staining. Nestin expression was related with tumor differentiation (P=0.036), lymphatic metastasis (N stage, P=0.011), and p-TNM stage (P=0.013), while there was no significant association between Nestin expression level and age, smoking habits, gender, histologic type, and T stage. Nestin was an independent prognostic factor for overall survival in NSCLC with an adjusted hazard ratio of 2.701 (95% CI, 1.616-4.513, P<0.001) after controlling the confounding factors. Then we determined the effects of Nestin on cell proliferation, colony formation, invasion, and apoptosis by knockout of Nestin with a new developed method, CRISPR/Cas9 mediated genome editing. It was observed that knockout of Nestin caused enhancement of cancer cell apoptosis and inhibition of cell proliferation, colony formation, and invasion in A549 and H1299 cell lines. Furthermore, we examined the expression of epithelial-mesenchymal transition (EMT) related biomarkers such as E-cadherin and Vimentin in Nestin-depleted lung cancer cells and knockout of Nestin was found to inhibit EMT, suggesting the involvement of Nestin mediated EMT signaling in lung cancer. The finding above demonstrated that Nestin might serve as a prognostic factor and therapeutic target in NSCLCs.