429 Background: The Gastric Cancer Registry (GCR) is a comprehensive resource that collects clinical information and samples from gastric cancer (GC) patients. The cancer samples undergo extensive molecular and cellular analysis that includes genomic sequencing, single cell and spatial analysis. Afterwards, this data is released through an online resource called the GCR Genome Explorer (GCR-GE) (https://gcregistry-explorer.stanford.edu/). We have added a single cell and spatial analysis data. Methods: The registry’s GC samples have been analyzed with whole genome, whole exome, and bulk RNA sequencing. As part of the latest data release, we have added several hundred GCs that have undergone either single cell or spatial transcriptomics analysis. We collected single cell RNA-seq (scRNA-seq) data from 208 samples from 118 patients. These data sets were generated in-house and downloaded from public datasets. Next, we developed a computational pipeline to mitigate batch effects in scRNA-seq data. This step involved applying generalized linear models, considering network properties and using sample level pseudo-aggregation. Finally, we used non-negative matrix factorization (NMF) to discover gene expression signatures characterizing the GC histologic subtypes. Results: We identified a diverse range of cell types, single cell gene expression profiles and cellular architecture in the context of the native tumor tissues. We focused on the cancer epithelial cells. The intestinal histologic subtype had highest overexpression of the Claudin gene family and JUN - FOS signaling. The diffuse histologic subtype had genes MUC1 and TFF1 were overly represented in diffuse subtype. Expression profiles were validated in an independent set of different GCs that consisted of 64 diffuse, 180 intestinal and 19 mixed cancers. The single cell data provides insight into the tumor microenvironment (TME). The diffuse subtype had higher prevalence of antibody secreting B cells, while intestinal subtype was enriched for pro inflammatory tumor associated macrophages. The intestinal subtype had increased regulatory T cells as an immunosuppressive mechanism. Diffuse GC had similar degree of CD8+ T cell abundance as intestinal GC. Using multiplex immunofluorescence, we identified TIGIT expression in CD8 and regulatory T cells in an independent cohort of 142 GC patients. Conclusions: By defining molecular and cellular characteristics across gastric cancers, this resource will accelerate research for identifying new treatment options such as distinct targetable features across different GC subtypes.
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