Clinicopathological significance of identifying glypican 3 -positive gastric cancer.

[OBJECTIVE] The aim of this study was to investigate the expression of Glypican 3 (GPC3) in gastric cancer and to identify clinicopathological prognostic factors associated with GPC3-positive gastric cancer (GPC3-GC).

[METHODS] Gene expression and survival differences of GPC3 were analyzed by the TCGA-STAD database and immunohistochemical detection in the gastric adenocarcinoma tissues.

[RESULTS] Bioinformatic analysis revealed that the GPC3 gene was highly expressed in gastric adenocarcinoma tissues (P < 0.05), and Univariate Cox regression analysis further demonstrated that the hazard ratio (HR) for GPC3 was 1.8 (95% CI: 1.3-2.5) (P < 0.001). Among the 218 cases of gastric adenocarcinoma tissue samples in this study, the positive rate of GPC3 was 17.0 % (37/218), increasing to 53.6 % (15/28) in cases with elevated serum AFP. Liver metastasis is more common in GPC3-positive gastric cancer (P < 0.001). GPC3-positive was more prevalent in adenocarcinomas with hepatoid or enteroblastic differentiation, depth of T3 + T4, clinical TNM stage III+IV (all P < 0.05). The Kaplan-Meier results revealed significant differences between the GPC3-negative and GPC3-positive groups (P < 0.001). However, no significant difference was found between GPC3-focal and diffuse tumors (P > 0.05). Cox regression analyses identified GPC3-positive as a risk factor affecting postoperative prognosis in gastric adenocarcinoma (P < 0.001). However, GPC3 can't serve as a prognostic indicator independent of other indicators (P > 0.05).

[CONCLUSION] GPC3 is expressed in some cases of gastric adenocarcinoma, particularly in cancers with elevated serum AFP levels, providing a potential basis for clinical monitoring and exploring new immunotherapy targets. GPC3-GC often exhibits strong invasive and metastatic capabilities and may carry a poor prognosis, especially in cases with enteroblastic differentiation and elevated serum AFP. Therefore, it is crucial to enhance awareness and differentiate GPC3-GC from common adenocarcinoma.