Cancer Med. 2026 Mar;15(3):e71711. doi: 10.1002/cam4.71711.
ABSTRACT
BACKGROUND AND AIMS: Microsatellite instability (MSI), programmed death-ligand 1 (PD-L1) expression, and Epstein-Barr virus (EBV) positivity are emerging biomarkers in gastric cancer prognosis and treatment selection, particularly in immunotherapy. This review evaluates their prognostic significance through a systematic review and meta-analysis.
METHODS: Relevant studies from PubMed, EMBASE, and the Cochrane Library (January 2010 to December 2024) were analyzed. Studies included assessing MSI, PD-L1, and EBV status in gastric cancer using immunohistochemistry, PCR, or in situ hybridization, and reported outcomes such as overall survival (OS), disease-free survival (DFS), or progression-free survival. Data extraction adhered to PRISMA guidelines, and pooled analyses were conducted using a random-effects model (DerSimonian-Laird method). Heterogeneity was assessed using I2 statistics and Cochran’s Q test.
RESULTS: A total of 25 studies involving 6494 patients were reviewed. In localized gastric cancer, MSI-high status was associated with significantly improved DFS (hazard ratio [HR], 0.42; 95% confidence interval [CI], 0.23-0.75; p = 0.004) but showed no significant impact on OS (HR, 0.78; 95% CI, 0.48-1.28; p = 0.33) compared to microsatellite stable/PD-L1-negative tumors. EBV-positive/PD-L1-positive cancers demonstrated a prognosis similar to EBV-negative/PD-L1-negative cases (OS: HR, 1.08; 95% CI, 0.81-1.45; p = 0.59).
CONCLUSIONS: In metastatic disease, MSI and EBV status were not associated with significant prognostic effects. MSI and EBV status have minimal prognostic value in gastric cancer, particularly for OS, but are essential for selecting candidates for immune checkpoint inhibitors. Standardizing biomarker evaluation is critical to enhancing their clinical relevance.
PMID:41856928 | DOI:10.1002/cam4.71711
