GPC2 provides prognostic value in pan-pediatric cancers and is associated with MYCN amplification in neuroblastoma：Bioinformatics Analysis and Validation

Background Glypican-2 (GPC2), a member of the GPC gene family, primarily functions in developing neural and thyroid cancer tissues, exerting influence on protein transduction, cellular proliferation and differentiation, as well as oncogenic signatures. GPC2 exhibits significant overexpression in the majority of neuroblastoma (NB) samples while remaining nearly undetectable in normal pediatric tissue samples. Methods Overall survival (OS) was employed as a key parameter to investigate the correlation between GPC2 expression and pan-pediatric cancers. To assess the association between GPC2 expression and clinical parameters of NB, box plots followed by t-tests were utilized. Protein-protein interaction (PPI) networks and gene-gene interaction networks were constructed. Functional roles were determined through Ontology (GO) term enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. The XCell was employed to analyze the relationship between GPC2 expression and immune-related cells. Additionally, we retrospectively collected clinical data and survival information from a cohort of 51 patients diagnosed with NB and conducted immunohistochemistry (IHC) on the specimens as a validation set. Results Except for osteosarcoma, high expression of GPC2 was significantly associated with lower survival rates in the remaining six pediatric tumors, particularly NB and brain tumors. Notably, the MYCN amplified group exhibited significantly higher levels of GPC2 expression. Furthermore, GPC2 expression showed a positive correlation with infiltrating basophils, CD4 T cells, CD8 T cells, CD8 naïve T cells, Tgd cells, Th1 cells, Th2 cells and pro B cells, while demonstrating a negative correlation with infiltrating fibroblasts, macrophages M1 and M2 subtypes, monocytes neutrophils and pDCs. Among all 51 pediatric NB patients analyzed in this study, the MYCN amplified group displayed significantly higher levels of GPC2 expression compared to the MYCN not-amplified group. Additionally, survival analysis revealed that individuals with high GPC2 expression had significantly worse OS compared to those with low expression (P = 0.018). Conclusion A significant correlation was observed between elevated GPC2 expression and reduced survival rates in six pediatric tumors, particularly in cases of NB and brain tumors. Furthermore, the expression level of GPC2 in NB showed a positive association with MYCN status and levels of immune cell infiltration.