Clinicopathological features and survival differences between G/GEJ-CSC and GAC: A Propensity score-matched, large-scale cross-population retrospective study

Abstract

Background and purpose

Gastric squamous cell carcinoma and adenosquamous carcinoma, collectively termed gastric and gastroesophageal junction carcinomas containing squamous cells (G/GEJ-CSC).Due to low incidence and high heterogeneity, their clinicopathological features and prognostic patterns lack systematic investigation. Traditional views suggest greater aggressiveness but lack large-scale evidence. This study uses large-scale cohorts to compare G/GEJ-CSC with gastric adenocarcinoma (GAC), clarifying features, prognosis, and supporting personalized treatment.

Methods

Retrospectively analyzed the clinicopathological features of eligible patients with G/GEJ-CSC and GAC from Zhejiang Cancer Hospital (2010–2024) and the SEER database (2004–2020). Propensity score matching was used to balance confounding factors. Kaplan-Meier method and Cox proportional hazards model were employed to evaluate survival differences.

Results

Compared with GAC patients, G/GEJ-CSC occurred more frequently in the gastric-esophageal junction and exhibited a significantly higher Epstein-Barr virus positivity rate, along with worse clinicopathological features. Multivariate Cox analysis showed that pathological type was an independent risk factor for overall survival (Chinese cohort:HR = 1.45,P = 0.044; SEER:HR = 1.23).Kaplan-Meier survival analysis revealed that OS was significantly inferior in G/GEJ-CSC patients compared with GAC (Chinese cohort: 5-year OS 33.0 % vs. 56.1 %, P < 0.001; SEER: 34.8 % vs. 42.7 %, P = 0.013), and this difference persisted after PSM adjustment (Chinese cohort: 5-year OS 36.4 % vs. 52.0 %, P = 0.034; SEER: 34.8 % vs. 44.1 %, P = 0.041). Stratified analysis further indicated a more pronounced survival gap in early-stage patients (Chinese cohort: 5-year OS43.1 % vs.84.1 %, P < 0.001; SEER: 45.4 % vs. 54.2 %, P = 0.002).

Conclusion

G/GEJ-CSC, a rare gastric cancer subtype, has unique aggressive biology and “early high-risk” prognosis. Need enhanced early identification and personalized treatment exploration.