Abstract 5304: Development of a plasma biomarker panel for gastric cancer detection based on an autoimmune response signature

Abstract Background: Gastric cancer is frequently diagnosed at an advanced stage and is associated with poor outcomes. Harnessing the immune response to tumor antigens which occurs early during tumor development has potential for the early detection of gastric cancer. Methods: Plasma samples from gastric cancer patients were collected before and after treatment and from healthy controls for identification of immunoglobin (Ig)-bound antigens using mass spectrometry. Ingenuity pathway analysis(IPA) was utilized to investigate networks and pathways associated with Ig bound proteins identified in plasmas from cases. A combined biomarker panel was established based on a logistic-regression model and ROC analysis was used to assess panel performance. Results: A total of 65 Ig bound proteins were identified that were upregulated in gastric cancer patients’ plasma compared with healthy control. Canonical pathways involving these immunogenic proteins included HIF-1α, VEGF, actin cytoskeleton, and immunogenic cell death signaling which play important roles in both gastric cancer development and progression. Four of the top ten performing proteins exhibited high mRNA levels in gastric cancer tissue. The association of these four Ig bound proteins in gastric cancer plasmas was further validated using as controls a cohort of MEN1 patients plasmas. A blood-biomarker panel based on these four biomarkers was established using a logistic-regression model which yielded an area under the curve (AUC) of 0.963 (95% confidential interval [CI] =0.89-1.00) for gastric cancer discrimination with a sensitivity of 0.889 at 95% specificity. Conclusion: Our data reveal a panel of plasma Ig-bound antigens associated with the development of gastric cancer with potential application for early detection and monitoring. Citation Format: Rongzhang Dou, Ehsan Irajizad, Yining Cai, Johannes F. Fahrmann, Jody V. Vykoukal, Yihui Chen, Hiroyuki Katayama, Ali H. Abdel Sater, Melissa Pizzi, Kohei Yamashita, Matheus Sewastjanow Da Silva, Edwin J. Ostrin, Jaffer Ajani, Samir M. Hanash. Development of a plasma biomarker panel for gastric cancer detection based on an autoimmune response signature. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5304.