Transcriptional expression of ZICs as an independent indicator of survival in gliomas

Sci Rep. 2021 Sep 2;11(1):17532. doi: 10.1038/s41598-021-93877-3.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Brain Neoplasms / genetics
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / mortality*
  • Brain Neoplasms / pathology
  • Computational Biology / methods
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Databases, Genetic
  • Databases, Protein
  • Gene Expression Regulation, Neoplastic
  • Glioblastoma / genetics
  • Glioblastoma / metabolism
  • Glioblastoma / mortality*
  • Glioblastoma / pathology
  • Glioma / genetics
  • Glioma / metabolism
  • Glioma / mortality*
  • Glioma / pathology
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Humans
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Prognosis
  • Survival Rate
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • Homeodomain Proteins
  • Nerve Tissue Proteins
  • Nuclear Proteins
  • Transcription Factors
  • ZIC1 protein, human
  • ZIC2 protein, human
  • ZIC3 protein, human
  • ZIC4 protein, human
  • ZIC5 protein, human