Comparison Of The Serum Proteome In Individuals With Cancers Versus Those Without Cancer, And Its Application To Wellness

For many diseases, pancreatic cancer for example, long term survival is critically dependent upon early detection. So various strategies for early detectable markers are being investigated. One such strategy is hypothesis driven, first by identifying a singular biomarker, usually derived from genomic analysis of the tumor type, and then determine its derivative protein concentration in blood. This has been challenging as many differentially regulated genes do not generate a differentially regulated protein, or one of sufficient concentration for current means of detection. An alternative biomarker strategy is purely data driven, as panels of proteins may be up and/or down regulated, or altered by post-translational modifications. These can be monitored and quantified to differences in diseased and normal/healthy individuals. In this study we adopt such a data driven strategy using a new product which combines Albumin depletion and on-bead digestion of the enriched serum proteome in a seamless process, called AlbuVoid™ LC-MS On-Bead. From these methods, we were able to compare labeled quantification of proteins from normal and disease state sera - for this case, breast, lung and pancreatic cancer at different clinically defined stages. The methods spectrally quantify over 250 total proteins, in a cost effective and reproducible manner. No offline peptide level fractionation prior to LC-MS was employed, lowering the LC-MS acquisition time 5-10x compared to common serum proteomic workflows. We describe these workflow advantages applied towards a “wellness” proteome algorithm combining knowledge and data surrounding individual normal and healthy proteomes, compared and contrasted to those with a clinically definable disease. From our initial tests, a candidate panel of 20 proteins are determined to be differentially expressed and such data suggests the feasibility for their use in the early detection of cancer. The critical parameters for success to our strategy are considered as well as some of the remaining challenges to clinical utility. Citation Format: Haiyan Zheng, Caifeng Zhao, Swapan Roy, Amenah Soherwardy, Ravish Amin, Devjit Roy, Matthew Kuruc. Comparison of the serum proteome in individuals with cancers versus those without cancer, and its application to wellness. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-065.