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Improved prediction of radiation pneumonitis by combining biological and radiobiological parameters using a data-driven Bayesian network analysis
Grade 2 and higher radiation pneumonitis (RP2) is a potentially fatal toxicity that limits efficacy of radiation therapy (RT). We wished to identify a combined biomarker signature of circulating miRNAs and cytokines which, along with radiobiological and clinical parameters, may better predict a targ...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Neoplasia Press
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9046881/ https://www.ncbi.nlm.nih.gov/pubmed/35460942 http://dx.doi.org/10.1016/j.tranon.2022.101428 |
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author | Hinton, Tonaye Karnak, David Tang, Ming Jiang, Ralph Luo, Yi Boonstra, Philip Sun, Yilun Nancarrow, Derek J. Sandford, Erin Ray, Paramita Maurino, Christopher Matuszak, Martha Schipper, Matthew J. Green, Michael D. Yanik, Gregory A. Tewari, Muneesh Naqa, Issam El Schonewolf, Caitlin A. Haken, Randall Ten Jolly, Shruti Lawrence, Theodore S. Ray, Dipankar |
author_facet | Hinton, Tonaye Karnak, David Tang, Ming Jiang, Ralph Luo, Yi Boonstra, Philip Sun, Yilun Nancarrow, Derek J. Sandford, Erin Ray, Paramita Maurino, Christopher Matuszak, Martha Schipper, Matthew J. Green, Michael D. Yanik, Gregory A. Tewari, Muneesh Naqa, Issam El Schonewolf, Caitlin A. Haken, Randall Ten Jolly, Shruti Lawrence, Theodore S. Ray, Dipankar |
author_sort | Hinton, Tonaye |
collection | PubMed |
description | Grade 2 and higher radiation pneumonitis (RP2) is a potentially fatal toxicity that limits efficacy of radiation therapy (RT). We wished to identify a combined biomarker signature of circulating miRNAs and cytokines which, along with radiobiological and clinical parameters, may better predict a targetable RP2 pathway. In a prospective clinical trial of response-adapted RT for patients (n = 39) with locally advanced non-small cell lung cancer, we analyzed patients’ plasma, collected pre- and during RT, for microRNAs (miRNAs) and cytokines using array and multiplex enzyme linked immunosorbent assay (ELISA), respectively. Interactions between candidate biomarkers, radiobiological, and clinical parameters were analyzed using data-driven Bayesian network (DD-BN) analysis. We identified alterations in specific miRNAs (miR-532, -99b and -495, let-7c, -451 and -139-3p) correlating with lung toxicity. High levels of soluble tumor necrosis factor alpha receptor 1 (sTNFR1) were detected in a majority of lung cancer patients. However, among RP patients, within 2 weeks of RT initiation, we noted a trend of temporary decline in sTNFR1 (a physiological scavenger of TNFα) and ADAM17 (a shedding protease that cleaves both membrane-bound TNFα and TNFR1) levels. Cytokine signature identified activation of inflammatory pathway. Using DD-BN we combined miRNA and cytokine data along with generalized equivalent uniform dose (gEUD) to identify pathways with better accuracy of predicting RP2 as compared to either miRNA or cytokines alone. This signature suggests that activation of the TNFα-NFκB inflammatory pathway plays a key role in RP which could be specifically ameliorated by etanercept rather than current therapy of non-specific leukotoxic corticosteroids. |
format | Online Article Text |
id | pubmed-9046881 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Neoplasia Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-90468812022-05-03 Improved prediction of radiation pneumonitis by combining biological and radiobiological parameters using a data-driven Bayesian network analysis Hinton, Tonaye Karnak, David Tang, Ming Jiang, Ralph Luo, Yi Boonstra, Philip Sun, Yilun Nancarrow, Derek J. Sandford, Erin Ray, Paramita Maurino, Christopher Matuszak, Martha Schipper, Matthew J. Green, Michael D. Yanik, Gregory A. Tewari, Muneesh Naqa, Issam El Schonewolf, Caitlin A. Haken, Randall Ten Jolly, Shruti Lawrence, Theodore S. Ray, Dipankar Transl Oncol Original Research Grade 2 and higher radiation pneumonitis (RP2) is a potentially fatal toxicity that limits efficacy of radiation therapy (RT). We wished to identify a combined biomarker signature of circulating miRNAs and cytokines which, along with radiobiological and clinical parameters, may better predict a targetable RP2 pathway. In a prospective clinical trial of response-adapted RT for patients (n = 39) with locally advanced non-small cell lung cancer, we analyzed patients’ plasma, collected pre- and during RT, for microRNAs (miRNAs) and cytokines using array and multiplex enzyme linked immunosorbent assay (ELISA), respectively. Interactions between candidate biomarkers, radiobiological, and clinical parameters were analyzed using data-driven Bayesian network (DD-BN) analysis. We identified alterations in specific miRNAs (miR-532, -99b and -495, let-7c, -451 and -139-3p) correlating with lung toxicity. High levels of soluble tumor necrosis factor alpha receptor 1 (sTNFR1) were detected in a majority of lung cancer patients. However, among RP patients, within 2 weeks of RT initiation, we noted a trend of temporary decline in sTNFR1 (a physiological scavenger of TNFα) and ADAM17 (a shedding protease that cleaves both membrane-bound TNFα and TNFR1) levels. Cytokine signature identified activation of inflammatory pathway. Using DD-BN we combined miRNA and cytokine data along with generalized equivalent uniform dose (gEUD) to identify pathways with better accuracy of predicting RP2 as compared to either miRNA or cytokines alone. This signature suggests that activation of the TNFα-NFκB inflammatory pathway plays a key role in RP which could be specifically ameliorated by etanercept rather than current therapy of non-specific leukotoxic corticosteroids. Neoplasia Press 2022-04-20 /pmc/articles/PMC9046881/ /pubmed/35460942 http://dx.doi.org/10.1016/j.tranon.2022.101428 Text en © 2022 The Authors. Published by Elsevier Inc. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Original Research Hinton, Tonaye Karnak, David Tang, Ming Jiang, Ralph Luo, Yi Boonstra, Philip Sun, Yilun Nancarrow, Derek J. Sandford, Erin Ray, Paramita Maurino, Christopher Matuszak, Martha Schipper, Matthew J. Green, Michael D. Yanik, Gregory A. Tewari, Muneesh Naqa, Issam El Schonewolf, Caitlin A. Haken, Randall Ten Jolly, Shruti Lawrence, Theodore S. Ray, Dipankar Improved prediction of radiation pneumonitis by combining biological and radiobiological parameters using a data-driven Bayesian network analysis |
title | Improved prediction of radiation pneumonitis by combining biological and radiobiological parameters using a data-driven Bayesian network analysis |
title_full | Improved prediction of radiation pneumonitis by combining biological and radiobiological parameters using a data-driven Bayesian network analysis |
title_fullStr | Improved prediction of radiation pneumonitis by combining biological and radiobiological parameters using a data-driven Bayesian network analysis |
title_full_unstemmed | Improved prediction of radiation pneumonitis by combining biological and radiobiological parameters using a data-driven Bayesian network analysis |
title_short | Improved prediction of radiation pneumonitis by combining biological and radiobiological parameters using a data-driven Bayesian network analysis |
title_sort | improved prediction of radiation pneumonitis by combining biological and radiobiological parameters using a data-driven bayesian network analysis |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9046881/ https://www.ncbi.nlm.nih.gov/pubmed/35460942 http://dx.doi.org/10.1016/j.tranon.2022.101428 |
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