Abstract
B‐cell translocation gene 2 (BTG2) is a tumour suppressor protein known to be downregulated in several types of cancer. In this study, we investigated a potential role for BTG2 in early‐stage non‐small cell lung cancer (NSCLC) survival. We analysed BTG2 methylation data from 1230 early‐stage NSCLC patients from five international cohorts, as well as gene expression data from 3038 lung cancer cases from multiple cohorts. Three CpG probes (cg01798157, cg06373167, cg23371584) that detected BTG2 hypermethylation in tumour tissues were associated with lower overall survival. The prognostic model based on methylation could distinguish patient survival in the four cohorts [hazard ratio (HR) range, 1.51–2.21] and the independent validation set (HR = 1.85). In the expression analysis, BTG2 expression was positively correlated with survival in each cohort (HR range, 0.28–0.68), which we confirmed with meta‐analysis (HR = 0.61, 95% CI 0.54–0.68). The three CpG probes were all negatively correlated with BTG2 expression. Importantly, an integrative model of BTG2 methylation, expression and clinical information showed better predictive ability in the training set and validation set. In conclusion, the methylation and integrated prognostic signatures based on BTG2 are stable and reliable biomarkers for early‐stage NSCLC. They may have new applications for appropriate clinical adjuvant trials and personalized treatments in the future.
Highlights
Lung cancer, predominantly non-small cell lung cancer (NSCLC), which constitutes more than 85% of all lung cancers, is the most commonly diagnosed malignant disease and is a leading cause of cancer-related deaths worldwide (Chen et al, 2014; Wood et al, 2016)
DNA methylation from B-cell translocation gene 2 (BTG2) is associated with lung cancer survival
We evaluated the association between the 13 CpG probes located in the BTG2 region and early-stage NSCLC overall survival in the training set including Harvard, Sweden, Spain and Norway cohorts
Summary
Predominantly non-small cell lung cancer (NSCLC), which constitutes more than 85% of all lung cancers, is the most commonly diagnosed malignant disease and is a leading cause of cancer-related deaths worldwide (Chen et al, 2014; Wood et al, 2016). Compared with patients diagnosed with late-stage disease, patients diagnosed with early-stage disease have a considerably more favourable prognosis, different prognoses still exist among patients with similar clinical characteristics (Hirsch et al, 2017). This phenomenon indicates the importance of improved understanding of genetic and molecular heterogeneity among these patients. In addition to the traditional molecular biomarkers, DNA methylation has improved our understanding of tumour genomics by identifying key biomarkers for multiple cancers and has played an important role in the development of targeted therapy (Bock et al, 2016; Jones et al, 2016)
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