IFI30 expression is an independent unfavourable prognostic factor in glioma

J Cell Mol Med. 2020 Nov;24(21):12433-12443. doi: 10.1111/jcmm.15758. Epub 2020 Sep 23.

Abstract

Gamma-interferon-inducible lysosomal thiol reductase, the only known lysosomal thiol reductase, is encoded by gene IFI30 and expressed constitutively in antigen-presenting cells. Our comprehensive study on IFI30 in gliomas found its expression to be high in glioblastomas and in gliomas with a mesenchymal subtype or wild-type isocitrate dehydrogenase, all of which indicated the malignancy and poor outcomes of gliomas. Kaplan-Meier survival analysis ascertained that high IFI30 expression conferred poor outcomes. The IFI30 expression levels also showed high efficiency in predicting 1-, 3- and 5-year overall survival. Univariable and multivariable Cox regression analyses were performed to define IFI30 as an independent prognostic marker. Biological process analysis suggested that IFI30 was involved in immune responses. ESTIMATE and CIBERSORT were applied to evaluate immune cell infiltration, with results indicating that samples with higher IFI30 expression had higher infiltration of immune cells, including regulatory T cells and M0 macrophages. Correlation analysis showed that IFI30 was significantly positively correlated with immune checkpoints that suppress effective antitumour immune responses. Immunohistochemical staining was also performed to confirm the association between IFI30 expression and the immune phenotype. The suggested correlation between high IFI30 expression and an immunosuppressive phenotype contributes to our knowledge about the glioma microenvironment and might provide clues for the development of novel therapeutic targets.

Keywords: IFI30; glioma; immune phenotype; prognostic factor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Brain Neoplasms / diagnosis
  • Brain Neoplasms / metabolism*
  • Cell Line, Tumor
  • Child
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Glioblastoma / pathology
  • Glioma / diagnosis
  • Glioma / metabolism*
  • Humans
  • Immune System
  • Isocitrate Dehydrogenase / genetics
  • Kaplan-Meier Estimate
  • Macrophages / metabolism
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Oxidoreductases Acting on Sulfur Group Donors / metabolism*
  • Phenotype
  • Prognosis
  • Proportional Hazards Models
  • Tumor Microenvironment
  • Young Adult

Substances

  • Isocitrate Dehydrogenase
  • IFI30 protein, human
  • Oxidoreductases Acting on Sulfur Group Donors