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  • Zhang, RuyangHarvard University,Nanjing Medical University,Nanjing University (author)

Independent Validation of Early-Stage Non-Small Cell Lung Cancer Prognostic Scores Incorporating Epigenetic and Transcriptional Biomarkers With Gene-Gene Interactions and Main Effects

  • Article/chapterEnglish2020

Publisher, publication year, extent ...

  • Elsevier BV,2020
  • 12 s.

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  • LIBRIS-ID:oai:lup.lub.lu.se:a120590c-3ffc-45aa-a01d-b850d9143f51
  • https://lup.lub.lu.se/record/a120590c-3ffc-45aa-a01d-b850d9143f51URI
  • https://doi.org/10.1016/j.chest.2020.01.048DOI

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  • Language:English
  • Summary in:English

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

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  • Background: DNA methylation and gene expression are promising biomarkers of various cancers, including non-small cell lung cancer (NSCLC). Besides the main effects of biomarkers, the progression of complex diseases is also influenced by gene-gene (G×G) interactions. Research Question: Would screening the functional capacity of biomarkers on the basis of main effects or interactions, using multiomics data, improve the accuracy of cancer prognosis? Study Design and Methods: Biomarker screening and model validation were used to construct and validate a prognostic prediction model. NSCLC prognosis-associated biomarkers were identified on the basis of either their main effects or interactions with two types of omics data. A prognostic score incorporating epigenetic and transcriptional biomarkers, as well as clinical information, was independently validated. Results: Twenty-six pairs of biomarkers with G×G interactions and two biomarkers with main effects were significantly associated with NSCLC survival. Compared with a model using clinical information only, the accuracy of the epigenetic and transcriptional biomarker-based prognostic model, measured by area under the receiver operating characteristic curve (AUC), increased by 35.38% (95% CI, 27.09%-42.17%; P = 5.10 × 10–17) and 34.85% (95% CI, 26.33%-41.87%; P = 2.52 × 10–18) for 3- and 5-year survival, respectively, which exhibited a superior predictive ability for NSCLC survival (AUC3 year, 0.88 [95% CI, 0.83-0.93]; and AUC5 year, 0.89 [95% CI, 0.83-0.93]) in an independent Cancer Genome Atlas population. G×G interactions contributed a 65.2% and 91.3% increase in prediction accuracy for 3- and 5-year survival, respectively. Interpretation: The integration of epigenetic and transcriptional biomarkers with main effects and G×G interactions significantly improves the accuracy of prognostic prediction of early-stage NSCLC survival.

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

  • Chen, ChaoNanjing Medical University (author)
  • Dong, XuesiHarvard University,Southeast University, Nanjing,Nanjing Medical University (author)
  • Shen, SipengNanjing Medical University,Harvard University (author)
  • Lai, LinjingNanjing Medical University (author)
  • He, JieyuNanjing Medical University (author)
  • You, DongfangHarvard University,Nanjing Medical University (author)
  • Lin, LijuanHarvard University,Nanjing Medical University (author)
  • Zhu, YingNanjing Medical University (author)
  • Huang, HuiNanjing Medical University (author)
  • Chen, JiajinNanjing Medical University (author)
  • Wei, LiangminNanjing Medical University (author)
  • Chen, XinNanjing Medical University (author)
  • Li, YiUniversity of Michigan (author)
  • Guo, YichenHarvard University (author)
  • Duan, WeiweiNanjing Medical University (author)
  • Liu, LiyaNingbo University (author)
  • Su, LiHarvard University (author)
  • Shafer, AndreaMassachusetts General Hospital,Harvard University (author)
  • Fleischer, ThomasOslo university hospital (author)
  • Moksnes Bjaanæs, MariaOslo university hospital (author)
  • Karlsson, AnnaLund University,Lunds universitet,Medicinsk strålningsfysik, Malmö,Forskargrupper vid Lunds universitet,Medical Radiation Physics, Malmö,Lund University Research Groups(Swepub:lu)rfa-aka (author)
  • Planck, MariaLund University,Lunds universitet,Forskningsgrupp Lungcancer,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Research Group Lung Cancer,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments(Swepub:lu)onk-mpl (author)
  • Wang, RuiJinling Hospital, Nanjing,Nanjing University (author)
  • Staaf, JohanLund University,Lunds universitet,Forskningsgrupp Lungcancer,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Research Group Lung Cancer,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments(Swepub:lu)onk-jst (author)
  • Helland, ÅslaugOslo university hospital,University of Oslo (author)
  • Esteller, ManelJosep Carreras Leukaemia Research Institute (IJC),University of Barcelona,Catalan Institution for Research and Advanced Studies,Spanish Center for Biomedical Research Network in Oncology (CIBERONC) (author)
  • Wei, YongyueNanjing Medical University,Harvard University (author)
  • Chen, FengNanjing Medical University (author)
  • Christiani, David C.Massachusetts General Hospital,Harvard University (author)
  • Harvard UniversityNanjing Medical University (creator_code:org_t)

Related titles

  • In:Chest: Elsevier BV158:2, s. 808-8190012-3692

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