Circulating proteome for pulmonary nodule malignancy

Abstract 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 differe...

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Published in:	JNCI : Journal of the National Cancer Institute Vol. 115; no. 9; pp. 1060 - 1070
Main Authors:	Khodayari Moez, Elham, Warkentin, Matthew T, Brhane, Yonathan, Lam, Stephen, Field, John K, Liu, Geoffrey, Zulueta, Javier J, Valencia, Karmele, Mesa-Guzman, Miguel, Nialet, Andrea Pasquier, Atkar-Khattra, Sukhinder, Davies, Michael P A, Grant, Benjamin, Murison, Kiera, Montuenga, Luis M, Amos, Christopher I, Robbins, Hilary A, Johansson, Mattias, Hung, Rayjean J
Format:	Journal Article
Language:	English
Published:	United States Oxford University Press 07-09-2023 Oxford Publishing Limited (England)
Subjects:	Benign Biomarkers Cancer screening Circulation Computed tomography Data systems Early Detection of Cancer Humans Lung - pathology Lung cancer Lung Neoplasms - diagnostic imaging Lung nodules Malignancy Medical screening Multiple Pulmonary Nodules - diagnostic imaging Multiple Pulmonary Nodules - pathology Nodules Proteins Proteome Proteomes Solitary Pulmonary Nodule - diagnostic imaging Solitary Pulmonary Nodule - pathology Statistical analysis Tomography Tumors
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Summary:	Abstract 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0027-8874 1460-2105 1460-2105
DOI:	10.1093/jnci/djad122