Integrated transcriptomic and clinical analyses reveal the prognostic relevance of GPC3 and a putative ceRNA-associated relationship in gastric cancer

To investigate the expression pattern and prognostic significance of glypican-3 (GPC3) in gastric cancer (GC) and identify its potential upstream non-coding RNA regulatory network. Transcriptomic data from TCGA-STAD and GEO datasets were used to compare GPC3 expression between GC and non-tumor gastric tissues, with validation using GEPIA. The prognostic value of GPC3 was evaluated using TCGA-STAD, GEPIA, and Kaplan–Meier Plotter. An independent clinical cohort from our center was included for immunohistochemical validation, and associations between GPC3 expression and clinicopathological features were assessed using chi-square or exact tests, as appropriate. Upstream miRNAs targeting GPC3 were predicted using starBase and screened by correlation and survival analyses. Candidate lncRNAs were further identified by integrating starBase and miRNet to identify a putative non-coding RNA regulatory relationship. GPC3 was significantly upregulated in GC tissues compared with non-tumor gastric tissues in TCGA-STAD, GSE33335, GSE54129, and GEPIA. High GPC3 expression was associated with worse overall survival and progression-free survival. In the independent cohort, GPC3 protein expression was elevated in GC tissues and showed exploratory associations with advanced T stage (P < 0.001), N stage (P = 0.014), TNM stage (P = 0.013), and perineural invasion (P = 0.041). Among 15 candidate miRNAs, hsa-miR-96-5p showed the strongest negative correlation with GPC3 (r=-0.32614, P < 0.001). LINC02381 was positively correlated with GPC3 (r = 0.30255, P < 0.001), negatively correlated with hsa-miR-96-5p (r=-0.15184, P < 0.01), and its high expression was associated with poor prognosis. GPC3 is overexpressed in GC and associated with poor prognosis. Bioinformatic analyses further suggested a putative LINC02381/miR-96-5p/GPC3 regulatory relationship associated with GPC3 expression in GC.