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Identification of a Biomarker Panel for Early Detection of Lung Cancer Patients
journal contribution
posted on 2019-08-21, 15:08 authored by Bethany Geary, Michael J. Walker, Joseph T. Snow, David 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, Anthony D. WhettonLung 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.
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Keywords
12 protein panelserum samplesmeasure proteinscontrol samplesmass spectrometry12 monthsstage IVlung cancer diagnosisprotein markersproteins effluxingSWATH-MS datalung cancer riskAUCBiomarker PanelSWATH-MS analysis11 protein marker panellung tumorsproteome signaturepatient samplesLung Cancer Patients Lung cancerSequential window acquisitionclassification modelcohortiTRAQ isobaricfragment ion spectra
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