Circulating proteome for pulmonary nodule malignancy
© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissionsoup.com..
BACKGROUND: Although lung cancer screening with low-dose computed tomography is rolling out in many areas of the world, differentiating indeterminate pulmonary nodules remains a major challenge. We conducted one of the first systematic investigations of circulating protein markers to differentiate malignant from benign screen-detected pulmonary nodules.
METHODS: Based on 4 international low-dose computed tomography screening studies, we assayed 1078 protein markers using prediagnostic blood samples from 1253 participants based on a nested case-control design. Protein markers were measured using proximity extension assays, and data were analyzed using multivariable logistic regression, random forest, and penalized regressions. Protein burden scores (PBSs) for overall nodule malignancy and imminent tumors were estimated.
RESULTS: We identified 36 potentially informative circulating protein markers differentiating malignant from benign nodules, representing a tightly connected biological network. Ten markers were found to be particularly relevant for imminent lung cancer diagnoses within 1 year. Increases in PBSs for overall nodule malignancy and imminent tumors by 1 standard deviation were associated with odds ratios of 2.29 (95% confidence interval: 1.95 to 2.72) and 2.81 (95% confidence interval: 2.27 to 3.54) for nodule malignancy overall and within 1 year of diagnosis, respectively. Both PBSs for overall nodule malignancy and for imminent tumors were substantially higher for those with malignant nodules than for those with benign nodules, even when limited to Lung Computed Tomography Screening Reporting and Data System (LungRADS) category 4 (P < .001).
CONCLUSIONS: Circulating protein markers can help differentiate malignant from benign pulmonary nodules. Validation with an independent computed tomographic screening study will be required before clinical implementation.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:115 |
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| Enthalten in: |
Journal of the National Cancer Institute - 115(2023), 9 vom: 07. Sept., Seite 1060-1070 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Khodayari Moez, Elham [VerfasserIn] |
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| Links: |
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| Themen: |
Journal Article |
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| Anmerkungen: |
Date Completed 08.09.2023 Date Revised 24.03.2024 published: Print Citation Status MEDLINE |
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| doi: |
10.1093/jnci/djad122 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM358703549 |
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| 100 | 1 | |a Khodayari Moez, Elham |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Circulating proteome for pulmonary nodule malignancy |
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| 500 | |a Date Revised 24.03.2024 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissionsoup.com. | ||
| 520 | |a BACKGROUND: Although lung cancer screening with low-dose computed tomography is rolling out in many areas of the world, differentiating indeterminate pulmonary nodules remains a major challenge. We conducted one of the first systematic investigations of circulating protein markers to differentiate malignant from benign screen-detected pulmonary nodules | ||
| 520 | |a METHODS: Based on 4 international low-dose computed tomography screening studies, we assayed 1078 protein markers using prediagnostic blood samples from 1253 participants based on a nested case-control design. Protein markers were measured using proximity extension assays, and data were analyzed using multivariable logistic regression, random forest, and penalized regressions. Protein burden scores (PBSs) for overall nodule malignancy and imminent tumors were estimated | ||
| 520 | |a RESULTS: We identified 36 potentially informative circulating protein markers differentiating malignant from benign nodules, representing a tightly connected biological network. Ten markers were found to be particularly relevant for imminent lung cancer diagnoses within 1 year. Increases in PBSs for overall nodule malignancy and imminent tumors by 1 standard deviation were associated with odds ratios of 2.29 (95% confidence interval: 1.95 to 2.72) and 2.81 (95% confidence interval: 2.27 to 3.54) for nodule malignancy overall and within 1 year of diagnosis, respectively. Both PBSs for overall nodule malignancy and for imminent tumors were substantially higher for those with malignant nodules than for those with benign nodules, even when limited to Lung Computed Tomography Screening Reporting and Data System (LungRADS) category 4 (P < .001) | ||
| 520 | |a CONCLUSIONS: Circulating protein markers can help differentiate malignant from benign pulmonary nodules. Validation with an independent computed tomographic screening study will be required before clinical implementation | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Proteome |2 NLM | |
| 700 | 1 | |a Warkentin, Matthew T |e verfasserin |4 aut | |
| 700 | 1 | |a Brhane, Yonathan |e verfasserin |4 aut | |
| 700 | 1 | |a Lam, Stephen |e verfasserin |4 aut | |
| 700 | 1 | |a Field, John K |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Geoffrey |e verfasserin |4 aut | |
| 700 | 1 | |a Zulueta, Javier J |e verfasserin |4 aut | |
| 700 | 1 | |a Valencia, Karmele |e verfasserin |4 aut | |
| 700 | 1 | |a Mesa-Guzman, Miguel |e verfasserin |4 aut | |
| 700 | 1 | |a Nialet, Andrea Pasquier |e verfasserin |4 aut | |
| 700 | 1 | |a Atkar-Khattra, Sukhinder |e verfasserin |4 aut | |
| 700 | 1 | |a Davies, Michael P A |e verfasserin |4 aut | |
| 700 | 1 | |a Grant, Benjamin |e verfasserin |4 aut | |
| 700 | 1 | |a Murison, Kiera |e verfasserin |4 aut | |
| 700 | 1 | |a Montuenga, Luis M |e verfasserin |4 aut | |
| 700 | 1 | |a Amos, Christopher I |e verfasserin |4 aut | |
| 700 | 1 | |a Robbins, Hilary A |e verfasserin |4 aut | |
| 700 | 1 | |a Johansson, Mattias |e verfasserin |4 aut | |
| 700 | 1 | |a Hung, Rayjean J |e verfasserin |4 aut | |
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