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

Shen, Sipeng; Zhang, Ruyang; Guo, Yichen; Loehrer, Elizabeth; Wei, Yongyue; Zhu, Ying; Yuan, Qianyu; Moran, Sebastian; Fleischer, Thomas and Bjaanæs, Maria M., et al. (2018) In Molecular Oncology
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... (More)

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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keywords
BTG2, Early-stage non-small cell lung cancer, Multi-omic, Prognosis
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Molecular Oncology
publisher
Elsevier
external identifiers
  • scopus:85046350166
ISSN
1574-7891
DOI
10.1002/1878-0261.12204
language
English
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yes
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d9dcc17c-3ff2-4b17-b5ee-ab4e0f0c35fc
date added to LUP
2018-05-17 13:10:39
date last changed
2018-10-03 10:31:51
@article{d9dcc17c-3ff2-4b17-b5ee-ab4e0f0c35fc,
  abstract     = {<p>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.</p>},
  author       = {Shen, Sipeng and Zhang, Ruyang and Guo, Yichen and Loehrer, Elizabeth and Wei, Yongyue and Zhu, Ying and Yuan, Qianyu and Moran, Sebastian and Fleischer, Thomas and Bjaanæs, Maria M. and Karlsson, Anna and Planck, Maria and Staaf, Johan and Helland, Åslaug and Esteller, Manel and Su, Li and Chen, Feng and Christiani, David C.},
  issn         = {1574-7891},
  keyword      = {BTG2,Early-stage non-small cell lung cancer,Multi-omic,Prognosis},
  language     = {eng},
  month        = {01},
  publisher    = {Elsevier},
  series       = {Molecular Oncology},
  title        = {A multi-omic study reveals BTG2 as a reliable prognostic marker for early-stage non-small cell lung cancer},
  url          = {http://dx.doi.org/10.1002/1878-0261.12204},
  year         = {2018},
}