Differential scanning calorimetry of blood plasma for lung cancer diagnosis.

Abstract

e21085 Background: We have invented a novel assay by using differential scanning calorimetry (DSC) for rapid characterization of the plasma proteome based on the thermal properties of the constituent proteins. Human plasma is a complex fluid that contains more than 3000 individual proteins and peptides in different quantities. DSC is a proven biophysical technique for measuring the energy absorbed by a solution of proteins as a function of temperature. The assay offers an entirely new analytical window into the plasma proteome, and provides a signature calorimetric thermogram that is a unique snapshot of an individual's plasma protein composition. Methods: Plasma samples were collected from lung cancer (LC) patients and healthy volunteers and stored at –70°C. Sample analysis was performed using an automated capillary DSC. Comparison of plasma thermograms from LC patients and controls was done using quantile-quantile plots and the Kolmogorov-Smirnov test. Results: Since our pilot study in 2009, we enrolled 60 LC patients but only analyzed 30 samples for this validation study plus another 109 normal controls. The thermograms from 109 control plasmas were highly reproducible and showed similar characteristic shape without statistical difference from our previous 100 control results. The samples from 30 new LC patients also yielded a unique thermogram differing from that of current and previous controls but similar to the results from 20 previous LC patients in our pilot study in 2009 without statistical difference. Our results further validated our hypothesis that DSC was sensitive to properties of the plasma proteins other than their charge and mass, and changes in thermogram shapes and positions in LC may arise from changes in the concentrations of plasma proteins, from disease-induced protein-protein interactions, or from the secretion into plasma of disease-related peptides or ligands that may bind to the most abundant plasma proteins. Conclusions: Lung cancer may have a characteristic signature thermogram that may serve as a biomarker. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Louisville Biosciences, Inc.