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Epigenetic modifica...
Epigenetic modifications inlysine demethylases associate with survival of early-stage NSCLC
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- Wei, Yongyue (författare)
- Harvard University
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- Liang, Junya (författare)
- Nanjing Medical University
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- Zhang, Ruyang (författare)
- Harvard University
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visa fler...
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- Guo, Yichen (författare)
- Harvard University
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- Shen, Sipeng (författare)
- Harvard University
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- Su, Li (författare)
- Nanjing Medical University
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- Lin, Xihong (författare)
- Harvard University
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- Moran, Sebastian (författare)
- Bellvitge University Hospital-IDIBELL
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- Helland, Åslaug (författare)
- Oslo university hospital
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- Bjaanæs, Maria M (författare)
- Oslo university hospital
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- Karlsson, Anna (författare)
- Lund University,Lunds universitet,Forskningsgrupp Lungcancer,Forskargrupper vid Lunds universitet,Research Group Lung Cancer,Lund University Research Groups
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- Planck, Maria (författare)
- Lund University,Lunds universitet,Forskningsgrupp Lungcancer,Forskargrupper vid Lunds universitet,Research Group Lung Cancer,Lund University Research Groups
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- Esteller, Manel (författare)
- Bellvitge University Hospital-IDIBELL
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- Fleischer, Thomas (författare)
- Oslo university hospital
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- Staaf, Johan (författare)
- Lund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Forskningsgrupp Lungcancer,Forskargrupper vid Lunds universitet,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Research Group Lung Cancer,Lund University Research Groups
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- Zhao, Yang (författare)
- Harvard University
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- Chen, Feng (författare)
- Harvard University
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- Christiani, David C (författare)
- Harvard University,Massachusetts General Hospital
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(creator_code:org_t)
- 2018-04-02
- 2018
- Engelska.
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Ingår i: Clinical Epigenetics. - : Springer Science and Business Media LLC. - 1868-7075 .- 1868-7083. ; 10
- Relaterad länk:
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http://dx.doi.org/10... (free)
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https://clinicalepig...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Background: KDMlysine demethylase family members are related to lung cancer clinical outcomes and are potential biomarkers for chemotherapeutics. However, little is known about epigenetic alterations inKDMgenes and their roles in lung cancer survival.Methods: Tumor tissue samples of 1230 early-stage non-small cell lung cancer (NSCLC) patients were collected from the five independent cohorts. The 393 methylation sites inKDMgenes were extracted from epigenome-wide datasets and analyzed by weighted random forest (Ranger) in discovery phase and validation dataset, respectively. The variable importance scores (VIS) for the sites in top 5% of both discovery and validation sets were carried forward for Cox regression to further evaluate the association with patient's overall survival. TCGA transcriptomic data were used to evaluate the correlation with the corresponding DNA methylation.Results: DNA methylation at sites cg11637544 inKDM2Aand cg26662347 inKDM1Awere in the top 5% of VIS in both discovery phase and validation for squamous cell carcinomas (SCC), which were also significantly associated with SCC survival (HRcg11637544 = 1.32, 95%CI, 1.16-1.50,P = 1.1 × 10-4;HRcg26662347 = 1.88, 95%CI, 1.37-2.60,P = 3.7 × 10-3), and correlated with corresponding gene expression (cg11637544 forKDM2A,P = 1.3 × 10-10; cg26662347 forKDM1A P = 1.5 × 10-5). In addition, by using flexible criteria for Ranger analysis followed by survival classification tree analysis, we identified four clusters for adenocarcinomas and five clusters for squamous cell carcinomas which showed a considerable difference of clinical outcomes with statistical significance.Conclusions: These findings highlight the association between somatic DNA methylation inKDMgenes and early-stage NSCLC patient survival, which may reveal potential epigenetic therapeutic targets.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Nyckelord
- Journal Article
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- art (ämneskategori)
- ref (ämneskategori)
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Wei, Yongyue
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Liang, Junya
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Zhang, Ruyang
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Guo, Yichen
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Shen, Sipeng
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Su, Li
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visa fler...
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Lin, Xihong
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Moran, Sebastian
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Helland, Åslaug
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Bjaanæs, Maria M
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Karlsson, Anna
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Planck, Maria
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Esteller, Manel
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Fleischer, Thoma ...
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Staaf, Johan
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Zhao, Yang
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Chen, Feng
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Christiani, Davi ...
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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Clinical Epigene ...
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Lunds universitet