Circulating Proteome for Pulmonary Nodule Malignancy.



Khodayari Moez, Elham, Warkentin, Matthew T, Brhane, Yonathan, Lam, Stephen, Field, John K ORCID: 0000-0003-3951-6365, Liu, Geoffrey, Zulueta, Javier J, Valencia, Karmele, Mesa-Guzman, Miguel, Nialet, Andrea Pasquier
et al (show 9 more authors) (2023) Circulating Proteome for Pulmonary Nodule Malignancy. Journal of the National Cancer Institute, 115 (9). djad122-djad122.

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Abstract

<h4>Background</h4>While lung cancer screening with low-dose computed tomography (LDCT) 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 versus benign screen-detected pulmonary nodules.<h4>Methods</h4>Based on four international LDCT screening studies, we assayed 1078 protein markers using pre-diagnostic 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 for overall nodule malignancy (PBS-overall) and imminent tumors (PBS-imminent) were estimated.<h4>Results</h4>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 one year. Increases in PBS-overall and PBS-imminent by 1 standard deviation were associated with odds ratios of 2.29(95%CI = 1.95-2.72), and 2.81(95%CI = 2.27-3.54) for nodule malignancy overall, and within 1 year of diagnosis, respectively. Both PBS-overall and PBS-imminent were substantially higher for those with malignant nodules compared to those with benign nodules even when limited to LungRADS category 4 (p < 0.001).<h4>Conclusions</h4>Circulating protein markers can help to differentiate malignant from benign pulmonary nodules. Validation with an independent CT-screening study will be required prior to clinical implementation.

Item Type: Article
Uncontrolled Keywords: Lung, Humans, Lung Neoplasms, Proteome, Solitary Pulmonary Nodule, Early Detection of Cancer, Multiple Pulmonary Nodules
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User: Symplectic Admin
Date Deposited: 18 Jul 2023 09:31
Last Modified: 15 Sep 2023 08:28
DOI: 10.1093/jnci/djad122
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3171670