Research progress of GPC3 and gastric cancer: Clinicopathologic characteristics and application prospects

The identification of new biomarkers and druggable targets is critical for improving the management of gastric cancer. Glypican-3 (GPC3), a glycosylphosphatidylinositol-anchored heparan sulfate proteoglycan, has emerged as a molecule of substantial translational interest due to its well-documented roles in tumorigenesis and its growing validation as a therapeutic target. Current research has found that GPC3 is expressed in some gastric adenocarcinomas and serves as a highly sensitive biomarker for alpha-fetoprotein-producing gastric cancer (AFPGC). GPC3 positivity is significantly correlated with adverse clinicopathologic features and poorer patient prognosis. As a key membrane-anchored biomarker, current research has identified GPC3 as a direct target for antibodies or cell therapies (such as CAR-T), with indications mainly focused on hepatocellular carcinoma, and it is also expected to provide a therapeutic approach for AFPGC and other solid cancers with abnormal expression of GPC3. Therefore, there is strong potential in identifying patients with GPC3-positive gastric cancer (GPC3-GC) for risk-stratified surveillance or enrollment in biomarker-guided therapeutic trials. However, current evidence on its clinicopathologic impact and clinical applicability in gastric cancer is fragmented and sometimes contradictory. This review systematically consolidates recent research progress to clarify the expression and prognostic significance of GPC3 in gastric cancer, explore its underlying molecular mechanisms, and evaluate its emerging promise as a target for novel therapies. Ultimately, we aim to bridge the gap between basic research and clinical practice, highlighting why GPC3 warrants focused investigation in the current gastric cancer research landscape.