Abstract 5142: Proteome-wide analysis identifies three subgroups of diffuse-type gastric cancer

Abstract

Abstract Background: Gastric cancer (GC) is highly heterogeneous and the leading cause of cancer death. Diffuse-type gastric cancer (DGC) is one of poor-prognosis GC subtypes with few treatment options. Genomic subtyping classifies overall gastric cancers into different subgroups that associate with prognosis and therapeutic targets, but it has not translated into clinical benefit. Proteomic subtyping with DGC may offer the potential for personalized risk stratification and treatment recommendation. Methods: We developed a workflow using fast mass spectrometry and ConsensusClusterPlus (CCP) consensus clustering for proteomic subtyping and applied it to 99 DGC formalin-fixed, paraffin-embedded (FFPE) samples. Results: In this study, 99 FFPE tumor samples were analyzed and classified into three proteomic subtypes (DGCP1-3) based on proteome-wide data, which were significantly associated with prognosis and response to chemotherapy. DGCP1 is with the best survival and DGCP3 is with the worst survival. DGCP2 derives benefit from chemotherapy. The rest of the subtypes do not receive benefit from chemotherapy. Specific signaling pathways are enriched in the subtypes: DGCP1/innate immune system; DGCP2/metabolism of RNA plus cell cycle; DGCP3/Extracellular Matrix (ECM). The classification with subtype-specific proteins provides a roadmap for stratifying patients into subgroups in trials of chemotherapy, targeted, and immune therapies. Conclusions: Proteomic subtyping of DGC identified three subgroups that have significant associations with distinct clinical characteristics. The DGCP subtyping can be further verified in more clinical cohorts and used to predict prognosis and recommend clinical actions in DGC treatment. Citation Format: Wenwen Huang, Xia Xia, Dongdong Zhan, Lin Shen, Jun Qin. Proteome-wide analysis identifies three subgroups of diffuse-type gastric cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5142.