Abstract

The functional significance of the zinc-finger of the cerebellum (ZIC) gene family in gliomas remains to be elucidated. Clinical data from patients with gliomas, containing expression levels of ZIC genes, were extracted from CCLE, GEPIA2 and The Human Protein Atlas (HPA). Univariate survival analysis adjusted by Cox regression via OncoLnc was used to determine the prognostic significance of ZIC expression. We used cBioPortal to explore the correlation between gene mutations and overall survival (OS). ZIC expression was found to be related to immune cell infiltration in gliomas via TIMER analysis. GO term and KEGG pathway enrichment analyzes were performed with Metascape. PPI networks were constructed using STRING. The expression levels of ZIC1/3/4/5 in gliomas were significantly different from those in normal samples. High expression levels of ZIC1/5 were associated with poor OS in brain low-grade glioma (LGG) patients, while low ZIC3 expression combined was related to favorable OS in glioblastoma multiforme (GBM). ZIC alterations were associated with poor prognosis in LGG patients and related to favorable prognosis in GBM patients. We observed that the expression of ZICs was related to immune cell infiltration in glioma patients. ZICs were enriched in several pathways and biological processes involving Neuroactive ligand-receptor interaction (hsa04080). The PPI network revealed that some proteins coexpressed with ZICs played a role in the pathogenesis of gliomas. Differences in the expression levels of ZIC genes could provide a significant marker for predicting prognosis in gliomas.

Highlights

  • The functional significance of the zinc-finger of the cerebellum (ZIC) gene family in gliomas remains to be elucidated

  • Significant upregulation of ZIC1/3/4 was found in brain low-grade glioma patients, while ZIC5 was downregulated

  • These results indicated that the mRNA expression of ZIC1/5 was a significant independent prognostic predictor for overall survival (OS) in low-grade glioma (LGG) patients, and the mRNA expression of ZIC3 was related to glioblastoma multiforme (GBM) patient prognosis, which suggested that ZIC1/5 and ZIC3 are independent prognostic factors in LGG and GBM patients, individually

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Summary

Introduction

The functional significance of the zinc-finger of the cerebellum (ZIC) gene family in gliomas remains to be elucidated. High expression levels of ZIC1/5 were associated with poor OS in brain low-grade glioma (LGG) patients, while low ZIC3 expression combined was related to favorable OS in glioblastoma multiforme (GBM). We observed that the expression of ZICs was related to immune cell infiltration in glioma patients. Abbreviations GBM Glioblastoma multiforme LGG Brain low-grade glioma CNS Central nervous system OS Overall survival PPI Protein–protein network GO Gene ontology KEGG Kyoto encyclopedia of genes and genomes ZIC Zinc-finger of the cerebellum. To determine the role of ZICs as prognostic biomarkers in LGG and GBM, we performed a comprehensive bioinformatics analysis using multiple datasets and further explored these data to identify the role of ZICs in glioma

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