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Sökning: id:"swepub:oai:lup.lub.lu.se:cc43223f-c21f-48c0-99d6-2a06a5be2c76" > A trans-omics asses...

A trans-omics assessment of gene–gene interaction in early-stage NSCLC

Chen, Jiajin (författare)
Nanjing Medical University
Song, Yunjie (författare)
Nanjing Medical University
Li, Yi (författare)
University of Michigan
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Wei, Yongyue (författare)
Nanjing Medical University,Harvard University
Shen, Sipeng (författare)
Nanjing Medical University
Zhao, Yang (författare)
Nanjing Medical University
You, Dongfang (författare)
Nanjing Medical University
Su, Li (författare)
Massachusetts General Hospital,Harvard University
Bjaanæs, Maria Moksnes (författare)
Oslo university hospital
Karlsson, Anna (författare)
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
Planck, Maria (författare)
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
Staaf, Johan (författare)
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
Helland, Åslaug (författare)
University of Oslo,Oslo university hospital
Esteller, Manel (författare)
University of Barcelona,Catalan Institution for Research and Advanced Studies,Josep Carreras Leukaemia Research Institute (IJC)
Shen, Hongbing (författare)
Nanjing Medical University
Christiani, David C. (författare)
Harvard University,Massachusetts General Hospital
Zhang, Ruyang (författare)
Nanjing Medical University,Harvard University
Chen, Feng (författare)
Nanjing Medical University
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 (creator_code:org_t)
2022-12-05
2023
Engelska 15 s.
Ingår i: Molecular Oncology. - : Wiley. - 1574-7891 .- 1878-0261. ; 17:1, s. 173-187
Relaterad länk:
http://dx.doi.org/10... (free)
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https://lup.lub.lu.s...
https://doi.org/10.1...
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  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
Stäng  
  • 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.

Ämnesord

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

Nyckelord

G × G interactions
NSCLC
overall survival
prognosis
trans-omics

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art (ämneskategori)
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