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Identification of a Biomarker Panel for Early Detection of Lung Cancer Patients

Geary, B; Walker, MJ; Snow, JT; Lee, DCH; Pernemalm, M; Maleki-Dizaji, S; Azadbakht, N; ... Whetton, AD; + view all (2019) Identification of a Biomarker Panel for Early Detection of Lung Cancer Patients. Journal of Proteome Research , 18 (9) pp. 3369-3382. 10.1021/acs.jproteome.9b00287. Green open access

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Abstract

Lung cancer is the most common cause of cancer-related mortality worldwide, characterized by late clinical presentation (49-53% of patients are diagnosed at stage IV) and consequently poor outcomes. One challenge in identifying biomarkers of early disease is the collection of samples from patients prior to symptomatic presentation. We used blood collected during surgical resection of lung tumors in an iTRAQ isobaric tagging experiment to identify proteins effluxing from tumors into pulmonary veins. Forty proteins were identified as having an increased abundance in the vein draining from the tumor compared to "healthy" pulmonary veins. These protein markers were then assessed in a second cohort that utilized the mass spectrometry (MS) technique: Sequential window acquisition of all theoretical fragment ion spectra (SWATH) MS. SWATH-MS was used to measure proteins in serum samples taken from 25 patients <50 months prior to and at lung cancer diagnosis and 25 matched controls. The SWATH-MS analysis alone produced an 11 protein marker panel. A machine learning classification model was generated that could discriminate patient samples from patients within 12 months of lung cancer diagnosis and control samples. The model was evaluated as having a mean AUC of 0.89, with an accuracy of 0.89. This panel was combined with the SWATH-MS data from one of the markers from the first cohort to create a 12 protein panel. The proteome signature developed for lung cancer risk can now be developed on further cohorts.

Type: Article
Title: Identification of a Biomarker Panel for Early Detection of Lung Cancer Patients
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1021/acs.jproteome.9b00287
Publisher version: https://doi.org/10.1021/acs.jproteome.9b00287
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: SRM, SWATH, biomarker, early detection, lung cancer, proteomics
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology > MRC Clinical Trials Unit at UCL
URI: https://discovery.ucl.ac.uk/id/eprint/10081406
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