Single-cell and bulk RNA-sequencing analysis reveals heterogeneity of PDPN in predicting prognosis and immunotherapy response of glioma

Abstract

Podoplanin (PDPN) is involved in various biological processes of tumors. We sought to investigate the heterogeneity of PDPN expression and the effect of PDPN on the immunological characteristics of gliomas. The signal-cell RNA sequencing (scRNA-seq) data was obtained from the GSE131928 dataset to investigate the heterogeneity of PDPN expression in GBMs. Bulk RNA-seq data of gliomas were obtained from the TCGA, CGGA325, CGGA693, and West China Hospital respectively. CIBERSORTx was used to identify infiltration of immune cells and TIDE was conducted to analyze the immunological function and immune checkpoint inhibitor (ICI) response. PDPN expression was positively associated with the malignancy and served as a predictor for worse overall survival of gliomas. Independent of isocitrate dehydrogenase (IDH) status, PDPN expression was associated with the increased infiltration of immunosuppressive immune cells. scRNA-seq data identified 7 core cell types in glioblastomas (GBMs) and revealed that MES-like GBM cells expressed the highest level of PDPN. AC-like and OPC-like GBM cells had a relatively higher expression of PDPN. Compared to relatively higher PDPN expression in monocytes and macrophages, normal oligodendrocytes and exhausted CD8 + T cells had the lowest level of PDPN. GBM cell clusters with different PDPN levels exhibited distinct functional pathways, such as tumor glycolysis, proliferation, and immune pathways. PDPN-upregulated gliomas were significantly associated with increased T lymphocyte dysfunction and exclusion and were more sensitive to ICI compared to PDPN-downregulated gliomas. Our results indicated that PDPN was heterogeneously expressed in GBMs and may facilitate guiding immunotherapy.