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A trans‐omics assessment of gene–gene interaction in early‐stage NSCLC
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...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9812838/ https://www.ncbi.nlm.nih.gov/pubmed/36408734 http://dx.doi.org/10.1002/1878-0261.13345 |
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author | Chen, Jiajin Song, Yunjie Li, Yi Wei, Yongyue Shen, Sipeng Zhao, Yang You, Dongfang Su, Li Bjaanæs, Maria Moksnes Karlsson, Anna Planck, Maria Staaf, Johan Helland, Åslaug Esteller, Manel Shen, Hongbing Christiani, David C. Zhang, Ruyang Chen, Feng |
author_facet | Chen, Jiajin Song, Yunjie Li, Yi Wei, Yongyue Shen, Sipeng Zhao, Yang You, Dongfang Su, Li Bjaanæs, Maria Moksnes Karlsson, Anna Planck, Maria Staaf, Johan Helland, Åslaug Esteller, Manel Shen, Hongbing Christiani, David C. Zhang, Ruyang Chen, Feng |
author_sort | Chen, Jiajin |
collection | PubMed |
description | 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 P (Bonferroni) ≤ 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 (β (interaction) = 0.018, P = 1.87 × 10(−12)), which mapped to RELA × HLA‐G (β (interaction) = 0.218, P = 8.82 × 10(−11)) and cg08872738 × cg27077312 (β (interaction) = −0.010, P = 1.16 × 10(−11)), which mapped to TUBA1B × TOMM40 (β (interaction) =−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. |
format | Online Article Text |
id | pubmed-9812838 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-98128382023-01-05 A trans‐omics assessment of gene–gene interaction in early‐stage NSCLC Chen, Jiajin Song, Yunjie Li, Yi Wei, Yongyue Shen, Sipeng Zhao, Yang You, Dongfang Su, Li Bjaanæs, Maria Moksnes Karlsson, Anna Planck, Maria Staaf, Johan Helland, Åslaug Esteller, Manel Shen, Hongbing Christiani, David C. Zhang, Ruyang Chen, Feng Mol Oncol Research Articles 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 P (Bonferroni) ≤ 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 (β (interaction) = 0.018, P = 1.87 × 10(−12)), which mapped to RELA × HLA‐G (β (interaction) = 0.218, P = 8.82 × 10(−11)) and cg08872738 × cg27077312 (β (interaction) = −0.010, P = 1.16 × 10(−11)), which mapped to TUBA1B × TOMM40 (β (interaction) =−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. John Wiley and Sons Inc. 2022-12-05 /pmc/articles/PMC9812838/ /pubmed/36408734 http://dx.doi.org/10.1002/1878-0261.13345 Text en © 2022 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Chen, Jiajin Song, Yunjie Li, Yi Wei, Yongyue Shen, Sipeng Zhao, Yang You, Dongfang Su, Li Bjaanæs, Maria Moksnes Karlsson, Anna Planck, Maria Staaf, Johan Helland, Åslaug Esteller, Manel Shen, Hongbing Christiani, David C. Zhang, Ruyang Chen, Feng A trans‐omics assessment of gene–gene interaction in early‐stage NSCLC |
title | A trans‐omics assessment of gene–gene interaction in early‐stage NSCLC
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title_full | A trans‐omics assessment of gene–gene interaction in early‐stage NSCLC
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title_fullStr | A trans‐omics assessment of gene–gene interaction in early‐stage NSCLC
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title_full_unstemmed | A trans‐omics assessment of gene–gene interaction in early‐stage NSCLC
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title_short | A trans‐omics assessment of gene–gene interaction in early‐stage NSCLC
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title_sort | trans‐omics assessment of gene–gene interaction in early‐stage nsclc |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9812838/ https://www.ncbi.nlm.nih.gov/pubmed/36408734 http://dx.doi.org/10.1002/1878-0261.13345 |
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