NANOG as an adverse predictive marker in advanced non–small cell lung cancer treated with platinum-based chemotherapy

PURPOSE NANOG is a master transcription factor that regulates stem cell pluripotency and cellular reprograming. Increased NANOG expression has been associated with poor survival in several human malignancies. However, the clinical significance of NANOG overexpression in lung cancer has been scarcely evaluated. The aim of this study was to investigate whether NANOG levels are associated with clinical outcomes of patients with non-small cell lung cancer (NSCLC) who were treated with platinum-based chemotherapy. METHODS NANOG levels were evaluated immunohistochemically using the histologic score (H-score) in tumor tissues from patients with advanced NSCLC who received platinum-based doublet treatment. We performed survival analyses according to the NANOG levels and evaluated the association between clinicopathological parameters and levels of NANOG. RESULTS Multivariate analyses using 112 tumor specimens showed that high NANOG levels were independently associated with short progression-free survival (hazard ratio [HR] =3.09, 95% confidence interval [CI]: 2.01-4.76) and with short overall survival (HR =3.00, 95% CI: 1.98-4.54). Similar results were shown in the subgroup analyses for patients with adenocarcinoma and squamous cell carcinoma. NANOG expression was not associated with any clinicopathological parameter such as age, gender, smoking status, stage, differentiation, or histological subtypes. CONCLUSION NANOG overexpression was associated with poor response and short overall survival in patients with advanced NSCLC who were treated with platinum-based chemotherapy, suggesting that NANOG could be a potential adverse predictive marker in this setting.