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A trans-omics asses...
A trans-omics assessment of gene–gene interaction in early-stage NSCLC
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- Chen, Jiajin (author)
- Nanjing Medical University
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- Song, Yunjie (author)
- Nanjing Medical University
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- Li, Yi (author)
- University of Michigan
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- Wei, Yongyue (author)
- Harvard University,Nanjing Medical University
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- Shen, Sipeng (author)
- Nanjing Medical University
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- Zhao, Yang (author)
- Nanjing Medical University
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- You, Dongfang (author)
- Nanjing Medical University
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- Su, Li (author)
- Massachusetts General Hospital,Harvard University
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- Bjaanæs, Maria Moksnes (author)
- Oslo university hospital
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- Karlsson, Anna (author)
- Lund University,Lunds universitet,Avdelningen för translationell cancerforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Forskningsgrupp Lungcancer,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Bröst/lungcancer,Sektion I,Institutionen för kliniska vetenskaper, Lund,Division of Translational Cancer Research,Department of Laboratory Medicine,Faculty of Medicine,Research Group Lung Cancer,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Breast/lungcancer,Section I,Department of Clinical Sciences, Lund
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- Planck, Maria (author)
- Lund University,Lunds universitet,Lungmedicin, allergologi och palliativ medicin,Sektion II,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Forskningsgrupp Lungcancer,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Bröst/lungcancer,Sektion I,Institutionen för kliniska vetenskaper, Lund,Respiratory Medicine, Allergology, and Palliative Medicine,Section II,Department of Clinical Sciences, Lund,Faculty of Medicine,Research Group Lung Cancer,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Breast/lungcancer,Section I,Department of Clinical Sciences, Lund
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- Staaf, Johan (author)
- Lund University,Lunds universitet,Avdelningen för translationell cancerforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Forskningsgrupp Lungcancer,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Bröst/lungcancer,Sektion I,Institutionen för kliniska vetenskaper, Lund,Division of Translational Cancer Research,Department of Laboratory Medicine,Faculty of Medicine,Research Group Lung Cancer,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Breast/lungcancer,Section I,Department of Clinical Sciences, Lund
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- Helland, Åslaug (author)
- Oslo university hospital,University of Oslo
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- Esteller, Manel (author)
- Josep Carreras Leukaemia Research Institute (IJC),Catalan Institution for Research and Advanced Studies,University of Barcelona
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- Shen, Hongbing (author)
- Nanjing Medical University
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- Christiani, David C. (author)
- Massachusetts General Hospital,Harvard University
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- Zhang, Ruyang (author)
- Harvard University,Nanjing Medical University
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- Chen, Feng (author)
- Nanjing Medical University
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(creator_code:org_t)
- 2022-12-05
- 2023
- English 15 s.
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In: Molecular Oncology. - : Wiley. - 1574-7891 .- 1878-0261. ; 17:1, s. 173-187
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Abstract
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- Epigenome-wide gene–gene (G × G) interactions associated with non-small-cell lung cancer (NSCLC) survival may provide insights into molecular mechanisms and therapeutic targets. Hence, we proposed a three-step analytic strategy to identify significant and robust G × G interactions that are relevant to NSCLC survival. In the first step, among 49 billion pairs of DNA methylation probes, we identified 175 775 G × G interactions with PBonferroni ≤ 0.05 in the discovery phase of epigenomic analysis; among them, 15 534 were confirmed with P ≤ 0.05 in the validation phase. In the second step, we further performed a functional validation for these G × G interactions at the gene expression level by way of a two-phase (discovery and validation) transcriptomic analysis, and confirmed 25 significant G × G interactions enriched in the 6p21.33 and 6p22.1 regions. In the third step, we identified two G × G interactions using the trans-omics analysis, which had significant (P ≤ 0.05) epigenetic cis-regulation of transcription and robust G × G interactions at both the epigenetic and transcriptional levels. These interactions were cg14391855 × cg23937960 (βinteraction = 0.018, P = 1.87 × 10−12), which mapped to RELA × HLA-G (βinteraction = 0.218, P = 8.82 × 10−11) and cg08872738 × cg27077312 (βinteraction = −0.010, P = 1.16 × 10−11), which mapped to TUBA1B × TOMM40 (βinteraction =−0.250, P = 3.83 × 10−10). A trans-omics mediation analysis revealed that 20.3% of epigenetic effects on NSCLC survival were significantly (P = 0.034) mediated through transcriptional expression. These statistically significant trans-omics G × G interactions can also discriminate patients with high risk of mortality. In summary, we identified two G × G interactions at both the epigenetic and transcriptional levels, and our findings may provide potential clues for precision treatment of NSCLC.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Keyword
- G × G interactions
- NSCLC
- overall survival
- prognosis
- trans-omics
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Chen, Jiajin
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Song, Yunjie
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Li, Yi
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Wei, Yongyue
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Shen, Sipeng
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Zhao, Yang
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You, Dongfang
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Su, Li
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Bjaanæs, Maria M ...
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Karlsson, Anna
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Planck, Maria
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Staaf, Johan
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Helland, Åslaug
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Esteller, Manel
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Shen, Hongbing
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Christiani, Davi ...
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Zhang, Ruyang
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Chen, Feng
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
- Articles in the publication
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Molecular Oncolo ...
- By the university
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Lund University