Molecular Profiles, Treatment-Associated Survival, and Prognosis in Early-Onset Versus Late-Onset Gastric Cancer: A Systematic Review and Meta-Analysis
- 1Department of General Surgery, West China Hospital, Sichuan University, Chengdu 610041, China
- 2Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy, Collaborative Innovation Center of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China
- 3Gastric Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China
Abstract
Background: Whether early-onset gastric cancer (EOGC) represents a distinct clinical entity requiring age-specific management remains uncertain. We synthesized molecular profiles, treatment-associated survival, and prognosis to determine what current evidence supports in practice and requires prospective validation. Methods: This PROSPERO-registered, PRISMA-compliant review searched four databases (PubMed, Web of Science Core Collection, Embase, and the Cochrane Library) from 1990 to 2025. Random-effects models compared EOGC with late-onset gastric cancer (LOGC) using each study’s reported age definition, provided that the upper age cutoff for EOGC did not exceed 50 years, and evaluated treatment–survival associations within EOGC. Robustness was evaluated by restricted maximum likelihood (REML) estimation with Knapp–Hartung adjustment, subgroup analyses, meta-regression, and prediction intervals; certainty was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE). Results: Fifty-eight studies involving 194,671 patients were included. EOGC showed lower observed odds of human epidermal growth factor receptor 2 (HER2) positivity (odds ratio [OR], 0.66; 95% confidence interval [CI], 0.53–0.84) and microsatellite instability (MSI)/deficient mismatch repair (dMMR) positivity (OR, 0.33; 95% CI, 0.12–0.91); p53 protein overexpression was less frequent, whereas the lower tumor protein p53 (TP53) mutation frequency represented only a non-significant numerical trend. E-cadherin loss was more frequent only under uniform immunohistochemical criteria (OR, 1.82; 95% CI, 1.16–2.85). These largely unadjusted molecular estimates indicate prevalence patterns rather than independent age effects. Radical resection was associated with lower mortality (hazard ratio [HR], 0.37; 95% CI, 0.22–0.61), but confounding by indication and a prediction interval crossing unity precluded causal inference. The chemotherapy association was not retained under REML–Knapp–Hartung analysis. Evidence was insufficient to establish differences in overall, disease-free, or cancer-specific survival. Certainty was low to very low. Conclusions: Age alone does not justify altered biomarker testing, systemic treatment, or surveillance. This review distinguishes actionable practice from unsupported extrapolation: established biomarker testing should be applied irrespective of age, and young age should not deter assessment for curative-intent resection. It also defines the evidence standards required before any EOGC-specific stratification can be adopted.
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BibTeX
@article{wen2026molecular,
title = {{Molecular Profiles, Treatment-Associated Survival, and Prognosis in Early-Onset Versus Late-Onset Gastric Cancer: A Systematic Review and Meta-Analysis}},
author = {Jianbin Wen and Linyong Zhao},
journal = {Journal of Clinical Medicine},
year = {2026},
month = oct,
doi = {10.3390/jcm15207814},
url = {https://www.mdpi.com/2077-0383/15/20/7814},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Molecular Profiles, Treatment-Associated Survival, and Prognosis in Early-Onset Versus Late-Onset Gastric Cancer: A Systematic Review and Meta-Analysis
AU - Jianbin Wen
AU - Linyong Zhao
PY - 2026
DA - 2026/10/10
JO - Journal of Clinical Medicine
DO - 10.3390/jcm15207814
UR - https://www.mdpi.com/2077-0383/15/20/7814
AB - Background: Whether early-onset gastric cancer (EOGC) represents a distinct clinical entity requiring age-specific management remains uncertain. We synthesized molecular profiles, treatment-associated survival, and prognosis to determine what current evidence supports in practice and requires prospective validation. Methods: This PROSPERO-registered, PRISMA-compliant review searched four databases (PubMed, Web of Science Core Collection, Embase, and the Cochrane Library) from 1990 to 2025. Random-effects models compared EOGC with late-onset gastric cancer (LOGC) using each study’s reported age definition, provided that the upper age cutoff for EOGC did not exceed 50 years, and evaluated treatment–survival associations within EOGC. Robustness was evaluated by restricted maximum likelihood (REML) estimation with Knapp–Hartung adjustment, subgroup analyses, meta-regression, and prediction intervals; certainty was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE). Results: Fifty-eight studies involving 194,671 patients were included. EOGC showed lower observed odds of human epidermal growth factor receptor 2 (HER2) positivity (odds ratio [OR], 0.66; 95% confidence interval [CI], 0.53–0.84) and microsatellite instability (MSI)/deficient mismatch repair (dMMR) positivity (OR, 0.33; 95% CI, 0.12–0.91); p53 protein overexpression was less frequent, whereas the lower tumor protein p53 (TP53) mutation frequency represented only a non-significant numerical trend. E-cadherin loss was more frequent only under uniform immunohistochemical criteria (OR, 1.82; 95% CI, 1.16–2.85). These largely unadjusted molecular estimates indicate prevalence patterns rather than independent age effects. Radical resection was associated with lower mortality (hazard ratio [HR], 0.37; 95% CI, 0.22–0.61), but confounding by indication and a prediction interval crossing unity precluded causal inference. The chemotherapy association was not retained under REML–Knapp–Hartung analysis. Evidence was insufficient to establish differences in overall, disease-free, or cancer-specific survival. Certainty was low to very low. Conclusions: Age alone does not justify altered biomarker testing, systemic treatment, or surveillance. This review distinguishes actionable practice from unsupported extrapolation: established biomarker testing should be applied irrespective of age, and young age should not deter assessment for curative-intent resection. It also defines the evidence standards required before any EOGC-specific stratification can be adopted.
SN - 2077-0383
ER -