Molecular and clinical characterization of PARP9 in gliomas: A potential immunotherapeutic target

CNS Neurosci Ther. 2020 Aug;26(8):804-814. doi: 10.1111/cns.13380. Epub 2020 Apr 24.

Abstract

Background: Glioma is a primary malignancy of the central nervous system (CNS). As biomedicine advances, an efficient molecular target is urgently needed for the diagnosis and treatment of glioma. Meanwhile, several studies have demonstrated that glioma development is closely related to immunity. PARP9 is an inactive mono-ADP-ribosyltransferase belonging to the poly-ADP ribosyltransferase (ARTD) family. In this article, we aimed to reveal the relationship between PARP9 and glioma and explore the potential prognostic value and immunotherapeutic targetability of PARP9 in glioma.

Methods: PARP9 transcript levels were analyzed with TCGA and GEO databases. The clinicopathological information of patients with glioma in the TCGA database and gene expression profiles were analyzed to determine the relationship between the expression of PARP9 and clinicopathologic characteristics. Kaplan-Meier survival analysis, univariate Cox regression analysis, and multivariate Cox regression analysis were used for survival analysis. Gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) were used for bioinformatics analysis. Correlation analysis explored the relationships between PARP9, infiltrating inflammatory immune cells, and immune checkpoint molecules.

Results: PARP9 is highly expressed in glioma, and high expression of PARP9 is associated with poor prognosis and advanced clinicopathological features. Bioinformatics analysis showed that some immune-related pathways were closely associated with high expression of PARP9. Correlation analysis indicated that PARP9 was closely related to inflammatory and immune responses, high immune cell infiltration, and immune checkpoint molecules.

Conclusions: PARP9 may serve as an unfavorable prognosis predictor for glioma and a potential immunotherapeutic target.

Keywords: PARP9; biomarker; glioma; immunotherapeutic targets; prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / biosynthesis*
  • Biomarkers, Tumor / genetics
  • Brain Neoplasms / genetics
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / therapy
  • Child
  • Databases, Genetic / trends
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Glioma / genetics
  • Glioma / metabolism*
  • Glioma / therapy
  • Humans
  • Immunotherapy / methods*
  • Immunotherapy / trends
  • Male
  • Middle Aged
  • Neoplasm Proteins / biosynthesis*
  • Neoplasm Proteins / genetics
  • Poly(ADP-ribose) Polymerases / biosynthesis*
  • Poly(ADP-ribose) Polymerases / genetics
  • Young Adult

Substances

  • Biomarkers, Tumor
  • Neoplasm Proteins
  • PARP9 protein, human
  • Poly(ADP-ribose) Polymerases