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  • Chen, JiajinNanjing Medical University (author)

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

  • Article/chapterEnglish2023

Publisher, publication year, extent ...

  • 2022-12-05
  • Wiley,2023
  • 15 s.

Numbers

  • LIBRIS-ID:oai:lup.lub.lu.se:cc43223f-c21f-48c0-99d6-2a06a5be2c76
  • https://lup.lub.lu.se/record/cc43223f-c21f-48c0-99d6-2a06a5be2c76URI
  • https://doi.org/10.1002/1878-0261.13345DOI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:art swepub-publicationtype
  • Subject category:ref swepub-contenttype

Notes

  • 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 and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Song, YunjieNanjing Medical University (author)
  • Li, YiUniversity of Michigan (author)
  • Wei, YongyueHarvard University,Nanjing Medical University (author)
  • Shen, SipengNanjing Medical University (author)
  • Zhao, YangNanjing Medical University (author)
  • You, DongfangNanjing Medical University (author)
  • Su, LiMassachusetts General Hospital,Harvard University (author)
  • Bjaanæs, Maria MoksnesOslo university hospital (author)
  • Karlsson, AnnaLund 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(Swepub:lu)med-akn (author)
  • Planck, MariaLund 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(Swepub:lu)onk-mpl (author)
  • Staaf, JohanLund 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(Swepub:lu)onk-jst (author)
  • Helland, ÅslaugOslo university hospital,University of Oslo (author)
  • Esteller, ManelJosep Carreras Leukaemia Research Institute (IJC),Catalan Institution for Research and Advanced Studies,University of Barcelona (author)
  • Shen, HongbingNanjing Medical University (author)
  • Christiani, David C.Massachusetts General Hospital,Harvard University (author)
  • Zhang, RuyangHarvard University,Nanjing Medical University (author)
  • Chen, FengNanjing Medical University (author)
  • Nanjing Medical UniversityUniversity of Michigan (creator_code:org_t)

Related titles

  • In:Molecular Oncology: Wiley17:1, s. 173-1871574-78911878-0261

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