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Identification of a Biomarker Panel for Early Detection of Lung Cancer Patients Bethany Geary, Michael J. Walker, Joseph T. Snow, Dave C.H. Lee, Maria Pernemalm, Saeedeh Maleki-Dizaji, Narges Azadbakht, Sophia Apostolidou, Julie Barnes, Piotr Krysiak, Rajesh Shah, Richard Booton, Caroline Dive, Philip A Crosbie, and Anthony D. Whetton J. Proteome Res., Just Accepted Manuscript • DOI: 10.1021/acs.jproteome.9b00287 • Publication Date (Web): 13 Aug 2019 Downloaded from pubs.acs.org on August 14, 2019
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Journal of Proteome Research
Identification of a Biomarker Panel for Early Detection of Lung Cancer Patients. Bethany Geary1,2, Michael J. Walker2, Joseph T. Snow2,3, David C. H. Lee1, Maria Pernemalm4, Saeedeh Maleki-Dizaji2, Narges Azadbakht2, Sophia Apostolidou5, Julie Barnes6, Piotr Krysiak7, Rajesh Shah7, Richard Booton8, Caroline Dive9,10, Philip A Crosbie1,5,8, Anthony D. Whetton1,3,10, *. 1 Stoller
Biomarker Discovery Centre, Institute of Cancer Sciences, Faculty of Medical and Human Sciences, University of Manchester, Manchester, United Kingdom 2 Stem cell and leukaemia proteomics laboratory, Institute of Cancer Sciences, Faculty of Medical and Human Sciences, University of Manchester, Manchester, United Kingdom 3 Department of Earth Sciences, University of Oxford, Oxford, United Kingdom. 4 Science for Life Laboratory, Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden. 5 Gynaecological Cancer Research Centre, Department of Women’s Cancer, Institute for Women’s Health, University College London, London, United Kingdom 6 Abcodia, Cambourne, Cambridgeshire, United Kingdom 7 Department of Thoracic Surgery, Wythenshawe Hospital, Manchester University NHS Foundation Trust, United Kingdom 8 North West Lung Centre, Wythenshawe Hospital, Manchester University NHS Foundation Trust, United Kingdom 9 Clinical and Experimental Pharmacology Group, Cancer Research UK Manchester Institute, University of Manchester, Manchester, United Kingdom 10 Cancer Research UK Lung Cancer Centre of Excellence
*
Corresponding author: Anthony D. Whetton
[email protected] +44 (0)161 2756267
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Abstract Lung cancer is the most common cause of cancer related mortality worldwide, characterised 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 tumours in an iTRAQ isobaric tagging experiment to identify proteins effluxing from tumours into pulmonary veins. 40 proteins were identified as having an increased abundance in the vein draining from the tumour compared to “healthy” pulmonary veins. These protein markers were then assessed in a second cohort that utilised 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
