LDH and glycolytic activity as predictors of immunotherapy response in gastric cancer: a systematic review and meta-analysis.

Abstract

<h4>Background</h4>Immune checkpoint inhibitors (ICIs) have transformed gastric cancer (GC) treatment, but response heterogeneity necessitates reliable prognostic biomarkers. This meta-analysis investigates the predictive value of metabolic (LDH, glycolytic activity) and inflammatory markers (NLR, PLR, LMR) in GC patients receiving ICIs.<h4>Methods</h4>We systematically analyzed 17 studies (n=3,842) from major databases through March 2024. Pooled hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) were calculated using random-effects models, with subgroup analyses by treatment type (monotherapy/combination). Study quality was assessed via Newcastle-Ottawa Scale.<h4>Results</h4>Elevated LDH significantly predicted poorer OS (HR=2.01, 95%CI:1.72-2.34) and PFS (HR=2.23, 95%CI:1.29-3.66), with minimal heterogeneity (I²=0%). Similarly, high NLR (HR=1.73) and PLR (HR=1.65) correlated with worse outcomes, while elevated LMR showed protection (HR=0.73). These associations remained consistent across treatment modalities and geographic regions (all Asian studies).<h4>Conclusions</h4>LDH and inflammatory markers are robust, clinically accessible prognostic biomarkers in GC immunotherapy. Their validation enables improved risk stratification and supports development of combination strategies targeting metabolic-immune crosstalk to enhance ICI efficacy.