Plasma thermogram profiling: A novel biomarker for lung cancer

Abstract

e22074 Background: Currently, there are no clinically useful biomarkers for lung cancer (LC). We developed a novel approach by using differential scanning calorimetry (DSC) to analyze the plasma proteome of LC patients. Our assay produces a signature snapshot of the plasma proteome based on the thermal properties of the constituent proteins within the mixture. Each individual protein has a unique and characteristic melting temperature and melting enthalpy. These biophysical properties are as intrinsic and unique for each protein as are its sequence, mass, and charge. The denaturation of plasma results in a composite signature thermogram that represents the sum of all of the individual proteins within the proteome, weighted according to their concentration within the plasma or serum. Our goal is to identify unique thermogram profiles as biomarkers for lung cancer evaluation. Methods: Plasma samples were collected from LC patients and healthy volunteers. Sample analysis was performed using an automated capillary DSC. Comparison of plasma thermograms from controls and diseased individuals was done using quantile-quantile plots and the Kolmogorov-Smirnov test. Results: One hundred samples were obtained from healthy volunteers. DSC thermograms from control plasma were highly reproducible and yielded a characteristic signature with a well-defined shape and temperature maxima. Twenty samples from LC patients were obtained at diagnosis. Plasma from LC individuals yielded a unique thermogram that differs from that of healthy controls. Preliminary results suggested that DSC was sensitive to properties of the plasma proteins other than their charge and mass. We hypothesize that changes in thermogram shapes and positions in LC can 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 that can bind to the most abundant plasma proteins. Conclusions: Lung cancer may have a characteristic signature thermogram that may serve as a biomarker for LC; further studies are needed to elucidate the biophysical and molecular mechanisms of different thermograms between normal individuals versus those with disease or cancer. No significant financial relationships to disclose.