Integrative analysis reveals the potential prognostic roles and immunological values of unc-5 netrin receptor A (UNC5A) in glioma.

ABSTRACT

BACKGROUND: UNC5A had been reported to play crucial roles in multiple cancers. However, little was known about the associations among UNC5A and glioma. Therefore, we first combined scRNA-seq, proteomics, as well as bulk RNA-seq in order to investigate UNC5A's functions in gliomas. METHODS: Online databases provided scRNA-seq, proteomics, as well as bulk RNA-seq data on UNC5A in gliomas. The following procedures were conducted in order QRT-PCR, Norman chart, gene set enrichment analysis (GSEA), and univariate/multifactor Cox regression analyses. We further explored the associations among UNC5A and tumor immunity. RESULTS: By comparing gliomas with normal tissues, the TCGA dataset showed a significantly reduced expression of UNC5A, which was also confirmed by GSE50161, GSE4290, and QRT-PCR findings (p < 0.05). In both the TCGA and CGGA datasets, gliomas patients with low-UNC5A expression would have poorer overall survival (OS) prognoses (p < 0.05). ScRNA-seq analysis by the CancerSEA online website presented that UNC5A had a low expression in various glioma clusters and significantly associated with six functional states. Moreover, UNC5A might be a reliable independent biomarker of OS in gliomas patients (p < 0.05). Based on the results of GSEA, UNC5A might be connected to three significant pathways in gliomas. We also successfully created a Norman chart to assess the OS prognoses of these patients. Additionally, in aspects of tumor immunity, the infiltration levels of immune cells in LGG, the immune cell pathways, tumor immune microenvironment, as well as immune checkpoints in both LGG and GBM were revealed to be significantly influenced by UNC5A (p < 0.05). CONCLUSIONS: UNC5A was found to have prognostic and immunological significance in gliomas, offering patients with gliomas new treatment options.