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

A multi-omic study reveals BTG2 as a reliable prognostic marker for early-stage non-small cell lung cancer.
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Shen S, Zhang R, Guo Y, Loehrer E, Wei Y, Zhu Y, Yuan Q, Moran S, Fleischer T, Bjaanaes MM, Karlsson A, Planck M, Staaf J, Helland Å, Esteller M, Su L, Chen F, Christiani DC,


Shen S, Zhang R, Guo Y, Loehrer E, Wei Y, Zhu Y, Yuan Q, Moran S, Fleischer T, Bjaanaes MM, Karlsson A, Planck M, Staaf J, Helland Å, Esteller M, Su L, Chen F, Christiani DC, (click to view)

Shen S, Zhang R, Guo Y, Loehrer E, Wei Y, Zhu Y, Yuan Q, Moran S, Fleischer T, Bjaanaes MM, Karlsson A, Planck M, Staaf J, Helland Å, Esteller M, Su L, Chen F, Christiani DC,

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Molecular oncology 2018 04 15() doi 10.1002/1878-0261.12204
Abstract

B-cell translocation gene 2 (BTG2) is a tumor suppressor protein and is 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 1,230 early-stage NSCLC patients from five international cohorts, as well as gene expression data from 3,038 lung cancer cases from multiple cohorts. Three CpG probes (cg01798157, cg06373167, cg23371584) that detected BTG2 hypermethylation in tumor 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 to 2.21] and the independent validation set (HR = 1.85). In the expression analysis, BTG2 expression positively correlated with survival in each cohort (HR range, 0.28 to 0.68), which we confirmed with meta-analysis (HR = 0.61, 95%CI: 0.54-0.68). The three CpG probes 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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