BJS 03 Comparative Analysis of Clinicopathological Features, Survival Outcomes, and Molecular Signatures between Adenocarcinomas of the Esophagogastric Junction and Gastric Adenocarcinoma
Min Lai, Jianling Zhang, Wenzhen YuanAbstract
Background
Although esophagogastric junction adenocarcinoma (AEGJ) and gastric adenocarcinoma (GAC) show distinct epidemiological and etiological features, their prognostic differences remain controversial. Comprehensive comparisons integrating clinical outcomes and molecular profiles are limited.
Methods
We compared clinicopathological characteristics, survival, and molecular features between AEGJ and GAC using the SEER database (2010–2021, n=14,193), an external validation cohort from Lanzhou University First Hospital (2017–2022, n=919), and TCGA transcriptomic data. Cox proportional hazards and Fine-Gray competing risk models assessed overall survival (OS) and cancer-specific survival (CSS). Differentially expressed genes (DEGs) between AEGJ and GAC in TCGA were used to construct a multi-gene prognostic risk model via LASSO and multivariate Cox regression.
Results
In the SEER cohort (AEGJ 6,338; GAC 7,855), AEGJ patients were more often White, younger (40–60 years), and diagnosed at stage II (P<0.001). AEGJ showed significantly worse 5-year OS (36% vs. 45%) and CSS (46% vs. 57%) than GAC (P<0.001), consistent across all TNM stages. Multivariable analysis confirmed higher mortality (HR=1.10) and cancer-specific mortality risk (subdistribution HR=1.20) in AEGJ (both P<0.001). External validation confirmed inferior OS in AEGJ overall and in stages I–III. The TCGA-derived gene risk model classified significantly more AEGJ patients as high-risk (60.6% vs. 41.8%, P=0.002), with high-risk status predicting poorer OS (P<0.0001).
Conclusion
AEGJ exhibits more aggressive clinicopathological and molecular features than GAC, resulting in consistently worse prognosis. These findings support treating AEGJ and GAC as distinct entities and highlight the need for tailored therapeutic strategies for AEGJ.