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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/174837
Independent validation of early-stage NSCLC prognostic scores incorporating epigenetic and transcriptional biomarkers with gene-gene interactions and main effects
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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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ZHANG, Ruyang, CHEN, Chao, DONG, Xuesi, SHEN, Sipeng, LAI, Linjing, HE, Jieyu, YOU, Dongfang, LIN, Lijuan, ZHU, Ying, HUANG, Hui, CHEN, Jiajin, WEI, Liangmin, CHEN, Xin, LI, Yi, GUO, Yichen, DUAN, Weiwei, LIU, Liya, SU, Li, SHAFER, Andrea, FLEISCHER, Thomas, BJAANÆS, Maria moksnes, KARLSSON, Anna, PLANCK, Maria, WANG, Rui, STAAF, Johan, HELLAND, Åslaug, ESTELLER, Manel, WEI, Yongyue, CHEN, Feng, CHRISTIANI, David c.. Independent validation of early-stage NSCLC prognostic scores incorporating epigenetic and transcriptional biomarkers with gene-gene interactions and main effects. _Chest_. 2020. Vol. 158, núm. 2, pàgs. 808-819. [consulta: 21 de gener de 2026]. ISSN: 0012-3692. [Disponible a: https://hdl.handle.net/2445/174837]