What does this research mean for the field?

Early-onset gastric cancer is clinically and genomically distinct from average-onset gastric cancer, presenting with more advanced disease stage, worse overall survival, and a higher frequency of CDH1 mutations. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

This research aims to understand the clinicopathologic and genomic differences between early-onset and average-onset gastric cancer.

May 30, 2026

Real-world clinicogenomic comparison of early- and average-onset gastric cancer.

Puntos clave

This research aims to understand the clinicopathologic and genomic differences between early-onset and average-onset gastric cancer.
Analyzed data from 311 patients using the ORIEN database.
Compared demographic, genomic, and survival outcomes between early-onset (EOGC) and average-onset (AOGC) gastric cancer.
Examined mutational and immune signatures via genomic sequencing.
EOGC patients had higher pain rates at diagnosis (53% vs 30%, p = 0.001).
EOGC patients more often presented with advanced stage disease (70% vs 45%, p = 0.006).
Decreased overall survival in EOGC (HR 1.52; p = 0.03) with unique patterns of somatic mutations, particularly CDH1.

Resumen

e16080 Background: In recent decades, there has been an unprecedented rise in gastric cancer among younger individuals, contrasting with a decline among older individuals. However, the biological underpinnings of gastric cancer in younger individuals remain poorly understood. We described the clinicopathologic and genomic characteristics of early-onset gastric cancer (EOGC) compared to average-onset gastric cancer (AOGC). Methods: We analyzed 311 patients using the multi-institutional prospective Oncology Research Information Exchange Network (ORIEN) database to compare demographic, clinicopathologic, genomic, and survival outcomes between EOGC ( 50 years N = 239). Genomic, germline, and RNA sequencing data were analyzed and compared between the cohorts. Mutational and immune signatures were also processed. Results: EOGC patients exhibited significantly higher rates of pain at diagnosis (53% vs 30% p = 0.001 ), but not anemia or reflux. EOGC patients were more likely to present with stage III/IV disease (70% vs 45% p = 0.006 ) and diffuse/signet ring histology (47% vs 16% p = 0.002 ). Consequently, OS was decreased in the younger cohort (HR 1.52; p = 0.03). Somatic mutational load was decreased in young patients. Significantly mutated genes in the entire cohort included CDH1 , ARID1A , TP53 , PIK3CA, but CDH1 was more frequently mutated in the EOGC cohort (40% vs 18% p = 0.006 ). Significant differences in RNA expression were observed, with upregulated epithelial mesenchymal transition (EMT), myogenesis, and apical junction. Immune deconvolution revealed a predominance of M2 macrophages, mast cells, and CD4 + T cell subsets, but no differences between cohorts. Conclusions: Early-onset gastric cancer has unique clinical and genomic features. Pathway dysregulation in EOGC may contribute to tumorigenesis and therapy resistance. This study underscores the necessity for further research into novel therapies, biomarker discovery, and early detection methodologies in younger individuals.

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