CALD1 Modulates Gliomas Progression via Facilitating Tumor Angiogenesis

SIMPLE SUMMARY: Caldesmon has recently attracted attention in cancer due to its roles in cell migration, invasion and proliferation. l-CALD1 was also considered a potential serum marker for glioma. However, little is known about mechanisms underlying the effect of CALD1 on the microvascular facilitation and architecture in glioma. The purpose of this study was to explore the role of CALD1 for prediction glioma patient prognosis and in glioma angiogenesis. The findings of this study suggested that l-CALD1 could imply abnormal microvessels in anaplastic astrocytoma and GBM. In addition, high CI (calmodulin index) predicted worse prognosis in glioma, and furthermore, CALD1 may serve as a key marker for monitoring the progress of glioma and a novel target for therapy. ABSTRACT: Angiogenesis is more prominent in anaplastic gliomas and glioblastoma (GBM) than that in pilocytic and diffuse gliomas. Caldesmon (CALD1) plays roles in cell adhesion, cytoskeletal organization, and vascularization. However, limited information is available on mechanisms underlying the effect of CALD1 on the microvascular facilitation and architecture in glioma. In this study, we explored the role of CALD1 in gliomas by integrating bulk RNA-seq analysis and single cell RNA-seq analysis. A positive correlation between CALD1 expression and the gliomas’ pathological grade was noticed, according to the samples from the TCGA and CGGA database. Moreover, higher CALD1 expression samples showed worse clinical outcomes than lower CALD1 expression samples. Biofunction prediction suggested that CALD1 may affect glioma progression through modulating tumor angiogenesis. The map of the tumor microenvironment also depicted that more stromal cells, such as endothelial cells and pericytes, infiltrated in high CALD1 expression samples. CALD1 was found to be remarkably upregulated in neoplastic cells and was involved in tumorigenic processes of gliomas in single cell sequencing analysis. Histology and immunofluorescence analysis also indicated that CALD1 associates with vessel architecture, resulting in glioma grade progression. In conclusion, the present study implies that CALD1 may serve as putative marker monitoring the progress of glioma.