Validation of the functions and prognostic values of synapse-associated proteins in lower-grade glioma

Biosci Rep. 2021 May 28;41(5):BSR20210391. doi: 10.1042/BSR20210391.

Abstract

Synapse and synapse-associated proteins (SAPs) play critical roles in various neurodegeneration diseases and brain tumors. However, in lower-grade gliomas (LGG), SAPs have not been explored systematically. Herein, we are going to explore SAPs expression profile and its clinicopathological significance in LGG which can offer new insights to glioma therapy. In the present study, we integrate a list of SAPs that covered 231 proteins with synaptogenesis activity and post synapse formation. The LGG RNA-seq data were downloaded from GEO, TCGA and CGGA database. The prognosis associated SAPs in key modules of PPI (protein-protein interaction networks) was regarded as hub SAPs. Western blot, quantitative reverse transcription PCR (qRT-PCR) and immunochemistry results from HPA database were used to verify the expression of hub SAPs. There were 68 up-regulated SAPs and 44 down-regulated SAPs in LGG tissue compared with normal brain tissue. Data from function enrichment analysis revealed functions of differentially expressed SAPs in synapse organization and glutamatergic receptor pathway in LGGs. Survival analysis revealed that four SAPs, GRIK2, GABRD, GRID2 and ARC were correlate with the prognosis of LGG patients. Interestingly, we found that GABRD were up-regulated in LGG patients with seizures, indicating that SAPs may link to the pathogenesis of seizures in glioma patients. The four-SAPs signature was revealed as an independent prognostic factor in gliomas. Our study presented a novel strategy to assess the prognostic risks of LGGs, based on the expression of SAPs.

Keywords: Synapse; lower-grade glioma; seizure; synapse associated protein.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Biomarkers, Tumor / standards*
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism
  • Gene Regulatory Networks
  • Glioma / genetics*
  • Glioma / metabolism
  • Glioma / pathology
  • GluK2 Kainate Receptor
  • Humans
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Predictive Value of Tests
  • Protein Interaction Maps
  • Receptors, GABA-A / genetics
  • Receptors, GABA-A / metabolism
  • Receptors, Glutamate / genetics
  • Receptors, Glutamate / metabolism
  • Receptors, Kainic Acid / genetics
  • Receptors, Kainic Acid / metabolism

Substances

  • Biomarkers, Tumor
  • Cytoskeletal Proteins
  • GABRD protein, human
  • Nerve Tissue Proteins
  • Receptors, GABA-A
  • Receptors, Glutamate
  • Receptors, Kainic Acid
  • activity regulated cytoskeletal-associated protein
  • glutamate receptor delta 2