P2.03b-040 NANOG Predicts Poor Outcome in Advanced Non-Small Cell Lung Cancer Patients Treated with Platinum-Based Chemotherapy: Topic: Biomarkers

Abstract

NANOG is a master transcription factor that regulates embryonic stem cell pluripotency and cell-fate specification though complex interaction with a myriad of factors in signaling pathways. Cumulating evidence suggests that it has oncogenic potential correlating with cell proliferation, clonogenic growth, tumorigenicity and invasiveness. Increased NANOG expression has been reported to be related with poor survival in several human malignancies including hepatic, breast, ovarian and colorectal cancers. However, clinical significance of NANOG overexpression in lung cancer has been scarcely evaluated, and correlation between NANOG expression and prognosis in advanced non-small cell lung cancer (NSCLC) has not been studied. The aim of this study is to investigate whether NANOG expression is associated with clinical outcomes of patients who were treated with platinum-based chemotherapy for advanced NSCLC. To prove NANOG overexpression in lung cancer, we initially assessed the expression of NANOG using Western blotting in lung cancer tissue from NSCLC patients who underwent surgical resection. Then, NANOG expression was examined by immunohistochemistry and evaluated by a semiquantitative histologic score (H score) in tumor tissues from NSCLC patients treated with platinum-based doublet. We performed survival analyses and evaluated the association between NANOG expression and clinical parameters. NANOG expression in lung cancer tissues was significantly increased compared with non-tumorous tissues (p < 0.001). Survival analyses using 110 tumor specimens showed that, at the cutoff value of H score 200, high NANOG expression was significantly associated with short progression-free survival (hazard ratio [HR] = 2.40, 95% confidence interval [CI]: 1.14 –5.62), and with short overall survival (HR = 2.89, 95% CI: 2.18–4.62). In addition, similar results were shown in the subgroup analyses for adenocarcinoma and squamous cell carcinoma. NANOG expression was not associated with any clinical parameter including age, gender, smoking status, stage, differentiation, or tumor histology. Increased NANOG expression was associated with poor response and short overall survival in advanced NSCLC patients treated with platinum-based chemotherapy. NANOG overexpression could be a potential adverse predictive marker in this setting.