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Title: A multi-omic study reveals BTG2 as a reliable prognostic marker for early-stage non-small cell lung cancer
Author: Shen, Sipeng
Zhang, Ruyang
Guo, Yichen
Loehrer, Elizabeth
Wei, Yongyue
Zhu, Ying
Yuan, Qianyu
Moran, Sebastian
Fleischer, Thomas
Bjaanaes, Maria M.
Karlsson, Anna
Planck, Maria
Staaf, Johan
Helland, Åslaug
Esteller, Manel
Su, Li
Chen, Feng
Christiani, David C.
Keywords: Càncer de pulmó
Proteïnes supressores de tumors
Lung cancer
Tumor suppressor protein
Issue Date: 4-May-2018
Publisher: Wiley
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.
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It is part of: Molecular Oncology, 2018, vol. 12, num. 6, p. 913-924
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Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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