Abstract LB-159: A multi-omic study reveals BTG2 as a reliable prognostic marker for early-stage non-small cell lung cancer

Abstract

Abstract Background B-cell translocation gene 2 (BTG2), which functions as a tumor suppress gene, has been reported to be involved in several cancers. However, no study has focused on its role in lung cancer progression or prognosis. We aimed to investigate the role of BTG2 in early-stage non-small cell lung cancer (NSCLC) survival. Patients and methods This study included 1,230 early-stage (1-2) surgically treated NSCLC patients with methylation and expression data from five international cohorts. We built a prognostic model based on methylation. Then, we explored BTG2 expression and NSCLC survival in 3,038 cases, including the above-mentioned cohorts as well as 17 extended public datasets by meta-analysis. Further, we integrated the clinical information, expression, and methylation to build an integration model and evaluated its prediction ability for 5-year survival. Results Three risk CpG probes (cg01798157, cg06373167, cg23371584) were associated with overall survival. The prognostic model could distinguish patient survival in the four cohorts [hazard ratio (HR) range, 1.51 to 2.21] and the independent validation set (HR = 1.85). In the expression analysis, BTG2 acted as a tumor-suppress gene in each cohort (HR range, 0.28 to 0.68). A meta-analysis showed high BTG2 expression was associated with better survival (HR = 0.61, 95%CI: 0.54-0.68). The three CpG probes were all negatively correlated with BTG2 expression. Additionally, the integration model showed a better prediction ability in the training set [area under the curve (AUC) = 0.78] and the validation set (AUC = 0.77). The integrated signature showed a better predictive ability among cases with adjuvant therapy (AUC = 0.85). In addition, 17 miRNAs including miR-21 and miR-23a were associated with BTG2 expression and survival. Conclusions: methylation and integrated prognostic signatures of BTG2 are stable and reliable biomarkers for early-stage NSCLC. These markers may have new applications for appropriate clinical adjuvant trials and personalized treatments in the future. Citation Format: Sipeng Shen, Li Su, Ruyang Zhang, Elizabeth Loehrer, Michael Lanuti, Nancy Diao, David Christiani. A multi-omic study reveals BTG2 as a reliable prognostic marker for early-stage non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-159.