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Open AccessArticle

Identification of a Blood-Based Protein Biomarker Panel for Lung Cancer Detection

1
Department of Oncology, Luxembourg Institute of Health, 1 A-B Rue Thomas Edison, L-1445 Strassen, Luxembourg
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Competence Center for Methodology and Statistics, Luxembourg Institute of Health, 1 A-B Rue Thomas Edison, L-1445 Strassen, Luxembourg
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Quantitative Biology Unit, Luxembourg Institute of Health, 1 A-B Rue Thomas Edison, L-1445 Strassen, Luxembourg
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Collaborative Center for Translational Mass Spectrometry, Translational Genomics Research Institute, 445 N Fifth St., Phoenix, AZ 85004, USA
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Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., Seattle, WA 98109-1024, USA
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Department of Cancer Biology, Mayo Clinic, 13400 E Shea Blvd, Scottsdale, AZ 85259, USA
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Norton Thoracic Institute, St. Joseph’s Hospital and Medical Center, Phoenix, AZ 85013, USA
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Department of cardiac surgery, Institut national de chirurgie cardiaque et de cardiologie interventionnelle, 2A rue Nicolas-Ernest Barblé, L-1210 Luxembourg, Luxembourg
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Zithaklinik, 46–48 rue d’Anvers, L-1130 Luxembourg, Luxembourg
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Department of Biomedicine, University of Bergen, Norway, Jonas Lies vei 91, N-5009 Bergen, Norway
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Centre Hospitalier de Luxembourg, 4 rue Nicolas-Ernest Barblé, L-1210 Luxembourg, Luxembourg
*
Author to whom correspondence should be addressed.
Present address: Centers for Disease Control and Prevention, 4770 Buford Hwy NE, Chamblee, GA 30341, USA.
Present address: Parker Institute for Cancer Immunotherapy, 1 Letterman Dr Suite D3500, Building D, San Francisco, CA 94129, USA.
§
Present address: SAP Concur, 601 108th Ave NE #1000, Bellevue, WA 98004 USA.
Present address: Adaptive Biotechnologies, 1551 Eastlake Ave E, Seattle, WA 98102, USA.
Present address: Nanjing AMADA AI LTD Company, Weier Road No. 7, Jiangning District, Nanjing, Jiangsu Province, Tangshan Street Industrial Concentration Area, n° 866 Nanpu Road, Yanjiang Street, Pukou district, Nanjing, Jiangsu 211132, China.
**
Present address: AstraZeneca, 1 Medimmune Way, Gaithersburg, MD 20878, USA.
Cancers 2020, 12(6), 1629; https://doi.org/10.3390/cancers12061629
Received: 10 May 2020 / Revised: 9 June 2020 / Accepted: 13 June 2020 / Published: 19 June 2020
(This article belongs to the Special Issue The Cancer Proteome)
Lung cancer is the deadliest cancer worldwide, mainly due to its advanced stage at the time of diagnosis. A non-invasive method for its early detection remains mandatory to improve patients’ survival. Plasma levels of 351 proteins were quantified by Liquid Chromatography-Parallel Reaction Monitoring (LC-PRM)-based mass spectrometry in 128 lung cancer patients and 93 healthy donors. Bootstrap sampling and least absolute shrinkage and selection operator (LASSO) penalization were used to find the best protein combination for outcome prediction. The PanelomiX platform was used to select the optimal biomarker thresholds. The panel was validated in 48 patients and 49 healthy volunteers. A 6-protein panel clearly distinguished lung cancer from healthy individuals. The panel displayed excellent performance: area under the receiver operating characteristic curve (AUC) = 0.999, positive predictive value (PPV) = 0.992, negative predictive value (NPV) = 0.989, specificity = 0.989 and sensitivity = 0.992. The panel detected lung cancer independently of the disease stage. The 6-protein panel and other sub-combinations displayed excellent results in the validation dataset. In conclusion, we identified a blood-based 6-protein panel as a diagnostic tool in lung cancer. Used as a routine test for high- and average-risk individuals, it may complement currently adopted techniques in lung cancer screening. View Full-Text
Keywords: lung cancer; plasma biomarker; targeted proteomics; parallel reaction monitoring; molecular diagnostics lung cancer; plasma biomarker; targeted proteomics; parallel reaction monitoring; molecular diagnostics
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El-Khoury, V.; Schritz, A.; Kim, S.-Y.; Lesur, A.; Sertamo, K.; Bernardin, F.; Petritis, K.; Pirrotte, P.; Selinsky, C.; Whiteaker, J.R.; Zhang, H.; Kennedy, J.J.; Lin, C.; Lee, L.W.; Yan, P.; Tran, N.L.; Inge, L.J.; Chalabi, K.; Decker, G.; Bjerkvig, R.; Paulovich, A.G.; Berchem, G.; Kim, Y.J. Identification of a Blood-Based Protein Biomarker Panel for Lung Cancer Detection. Cancers 2020, 12, 1629.

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