Development of a plasma biomarker panel for gastric cancer detection based on an autoimmune response signature

e16101 Background: Gastric cancer is frequently diagnosed at an advanced stage and is associated with poor outcomes. A humoral immune response to tumor antigens in the form of autoantibodies occurs early during tumor development. Harnessing autoantibodies and corresponding antigens has potential for diagnostic and therapeutics applications. Methods: Plasma samples from gastric cancer patients were collected before treatment and from non-gastric cancer cases and healthy controls for identification and quantitative analysis of immunoglobin (Ig)-bound antigens using mass spectrometry. The Ig-bound antigens were pulled down with a Protein A/G column for analysis by mass spectrometry. A protein A/G plate capture enzyme-linked immunosorbent assay (ELISA) was developed to validate Ig-bound MS results. A combined biomarker panel was established based on a logistic-regression model and ROC analysis was used to assess panel performance. Results: From a total of 983 proteins identified from gastric cancer samples, four Ig bound proteins were found to be enriched in gastric cancer plasmas compared with healthy controls and plasmas from other cancer types which yielded an area under the curve (AUC) of 0.973 (95% confidential interval [CI] = 0.92-1.00) for gastric cancer discrimination with a sensitivity of 0.91 at 95% specificity. Enzyme-linked immunosorbent assay (ELISA) based data yielded a high correlation (r = 0.72, P = 0.0199) with Ig-bound mass spectrometry data. These four proteins were found to be highly expressed in gastric cancer based on TCGA transcriptomic data with concordant tumor cell proteomic data. Conclusions: Our data reveal a panel of plasma Ig-bound antigens associated with the development of gastric cancer with potential application for gastric cancer detection and monitoring and potential therapeutic relevance.