SERUM PROTEOMIC BIOMARKERS FOR LUNG CANCER DETECTION AND PROGNOSIS

University Of Pittsburgh At Pittsburgh, Pittsburgh PA

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Abstract

Project 3, a new SPORE project initiated using Developmental Research Program support in the present[unreadable] SPORE, will utilize the state-of-the-art Bruker ClinProtTM Ultraflexll MALDI TOF/TOF mass spectrometry[unreadable] (MS) and Luminex multianalyte (LabMAP(R)) systems to profile serum samples from an extensive population[unreadable] of SPORE accrued lung cancer patients and controls. First we will develop a panel of proteomic MS[unreadable] features reproducibly detectable in serum together with optimized panels of known serum analytes relevant[unreadable] to lung cancer including cytokines, chemokines, growth/angiogenesis factors and receptors, and lung[unreadable] specific biomarkers, to provide robust detection and discrimination of lung cancer. This combined[unreadable] MS/LabMAP(R) serum proteomic panel and predictive lung cancer model will then be tested in an[unreadable] independent series of case/controls sera in collaboration with the Vanderbilt Lung SPORE and in a series of[unreadable] screening CT-detected lung Cancers in the UPCI SPORE PLuSS cohort. The refined MS/ LabMAP(R) panel[unreadable] and predictive model will be tested in a prospectively collected series of serum samples from subjects in the[unreadable] PLuSS High-Risk Sub-Cohort subsequently diagnosed with a newly-incident CT-detected lung cancer during[unreadable] a 5-year active follow-up. To test the power of this proteomic approach to predict lung cancer recurrence,[unreadable] the UPCI case series will be followed prospectively by the SPORE Clinical Core for recurrence, disease[unreadable] progression, and survival. The baseline MALDI-TOF-MS proteomic profiles and MS/LabMAP(R) panel will[unreadable] then be evaluated and a model constructed to predict these clinical outcomes. The predictive recurrence[unreadable] model will then be tested in the Vanderbilt Lung Cancer SPORE cases. Lastly, in parallel with these aims,[unreadable] diagnostic MS features ("peaks") will be investigated for peptide/protein identification using a suite of[unreadable] biochemical enrichment/fractionation and MS analytical methods for lung cancer biomarker discovery. The[unreadable] translational goals of Project 3 are to develop a MS/LabMAP(R) serum profile and predictive algorithm to[unreadable] provide improved diagnosis of patients presenting with clinical symptoms or radiographic findings suspicious[unreadable] for lung cancer; to improve early detection of lung cancer by identifying a MS/LabMAP(R) serum profile in[unreadable] high-risk subjects prior to the clinical diagnosis of a lung malignancy by screening CT; and the application of[unreadable] MS/LabMAP(R) serum profiling for prediction and early detection of lung cancer recurrence.