Multi-omic characterization of early-onset esophagogastric cancer

Using a large real-world database with matched genomic and transcriptomic data, we characterized clinical and molecular differences between patients with early-onset esophagogastric cancer (EOEGC; <50 years), intermediate-onset esophagogastric cancer (IOEGC; 50-65 years), and average-onset esophagogastric cancer (AOEGC; >65 years). We analyzed clinicopathologic, whole transcriptome, and DNA-sequencing data from 5175 patient samples (EOEGC, n = 530; IOEGC, n = 1744; AOEGC, n = 2901) from the Caris Life Sciences database. Immune deconvolution was performed with quanTIseq and pathway enrichment with Gene Set Enrichment Analysis (GSEA). Real-world overall survival was estimated from insurance claims data. Prevalence of EOEGC was higher in patients who were Black, Asian, Hispanic/Latino, and female. Patients with EOEGC had higher proportion of CDH1 mutations; FGFR2, CCNE1, MYC copy number alterations; and ARHGAP26 fusions. Patients with EOEGC had decreased prevalence of immune-oncology markers of microsatellite instability-high, tumor mutation burden-high, and PD-L1 positivity. Immune microenvironment analysis identified significant enrichment of M2 macrophages and decreased M1 macrophages in patients with EOEGC. GSEA identified enrichment of epithelial mesenchymal transition and coagulation pathways in patients with EOEGC. This large real-world characterization of age-stratified esophagogastric cancer found that EOEGC was associated with significant racial, ethnic, and gender differences, and notable molecular differences that may have prognostic and therapeutic implications.