Circulating proteome for pulmonary nodule malignancy.
Elham Khodayari Moez, Matthew T Warkentin, Yonathan Brhane, Stephen Lam, John K Field, Geoffrey Liu, Javier J Zulueta, Karmele Valencia, Miguel Mesa-Guzman, Andrea Pasquier Nialet, Sukhinder Atkar-Khattra, Michael P A Davies, Benjamin Grant, Kiera Murison, Luis M Montuenga, Christopher I Amos, Hilary A Robbins, Mattias Johansson, Rayjean J Hung
Author Information
Elham Khodayari Moez: Prosserman Centre for Population Health Research, Lunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, ON, Canada. ORCID
Matthew T Warkentin: Prosserman Centre for Population Health Research, Lunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, ON, Canada. ORCID
Yonathan Brhane: Prosserman Centre for Population Health Research, Lunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, ON, Canada. ORCID
Stephen Lam: Integrative Oncology, British Columbia Cancer Agency, Vancouver, BC, Canada.
John K Field: Molecular & Clinical Cancer Medicine, University of Liverpool, Liverpool, UK.
Geoffrey Liu: Computational Biology and Medicine Program, Princess Margaret Cancer Center, Toronto, ON, Canada. ORCID
Javier J Zulueta: Division of Pulmonary, Critical Care and Sleep Medicine, Mount Sinai Morningside Hospital, Icahn School of Medicine, New York, NY, USA. ORCID
Karmele Valencia: Center of Applied Medical Research (CIMA) and Schools of Sciences and Medicine, University of Navarra, Pamplona, Spain. ORCID
Miguel Mesa-Guzman: Thoracic Surgery Department, Cl��nica Universidad de Navarra, Pamplona, Spain.
Andrea Pasquier Nialet: Center of Applied Medical Research (CIMA) and Schools of Sciences and Medicine, University of Navarra, Pamplona, Spain.
Sukhinder Atkar-Khattra: Integrative Oncology, British Columbia Cancer Agency, Vancouver, BC, Canada. ORCID
Michael P A Davies: Molecular & Clinical Cancer Medicine, University of Liverpool, Liverpool, UK.
Benjamin Grant: Computational Biology and Medicine Program, Princess Margaret Cancer Center, Toronto, ON, Canada.
Kiera Murison: Prosserman Centre for Population Health Research, Lunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, ON, Canada.
Luis M Montuenga: Center of Applied Medical Research (CIMA) and Schools of Sciences and Medicine, University of Navarra, Pamplona, Spain.
Christopher I Amos: Institute for Clinical and Translational Research, Baylor College of Medicine, Houston, TX, USA.
Hilary A Robbins: Genomic Epidemiology Branch, International Agency for Research on Cancer, Lyon, France. ORCID
Mattias Johansson: Genomic Epidemiology Branch, International Agency for Research on Cancer, Lyon, France. ORCID
Rayjean J Hung: Prosserman Centre for Population Health Research, Lunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, ON, Canada. ORCID
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 benignpulmonary nodules. Validation with an independent computed tomographic screening study will be required before clinical implementation.
References
Cancers (Basel). 2021 Feb 15;13(4):
[PMID: 33671847]
