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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 (author)
Nanjing Medical University,Harvard University
Zhang, Ruyang (author)
Nanjing Medical University
Guo, Yichen (author)
Harvard University
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Loehrer, Elizabeth (author)
Harvard University
Wei, Yongyue (author)
Nanjing Medical University
Zhu, Ying (author)
Nanjing Medical University
Yuan, Qianyu (author)
Harvard University
Moran, Sebastian (author)
University of Barcelona
Fleischer, Thomas (author)
Oslo university hospital
Bjaanæs, Maria M. (author)
Oslo university hospital
Karlsson, Anna (author)
Lund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine
Planck, Maria (author)
Lund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine
Staaf, Johan (author)
Lund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine
Helland, Åslaug (author)
University of Oslo,Oslo university hospital
Esteller, Manel (author)
University of Barcelona
Su, Li (author)
Nanjing Medical University,Harvard University
Chen, Feng (author)
Nanjing Medical University
Christiani, David C. (author)
Harvard Medical School,Harvard University,Nanjing Medical University
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 (creator_code:org_t)
2018-05-04
2018
English.
In: Molecular Oncology. - : Wiley. - 1574-7891 .- 1878-0261. ; 12:6, s. 913-924
  • Journal article (peer-reviewed)
Abstract Subject headings
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  • 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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

Keyword

BTG2
Early-stage non-small cell lung cancer
Multi-omic
Prognosis

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