Collagen Type III Alpha 1 chain regulated by GATA-Binding Protein 6 affects Type II IFN response and propanoate metabolism in the recurrence of lower grade glioma

J Cell Mol Med. 2020 Sep;24(18):10803-10815. doi: 10.1111/jcmm.15705. Epub 2020 Aug 5.

Abstract

Some studies suggested the prognosis value of immune gene in lower grade glioma (LGG). Recurrence in LGG is a tough clinical problem for many LGG patients. Therefore, prognosis biomarker is required. Multivariate prognosis Cox model was constructed and then calculated the risk score. And differential expressed transcription factors (TFs) and differential expressed immune genes (DEIGs) were co-analysed. Besides, significant immune cells/pathways were identified by single sample gene set enrichment analysis (ssGSEA). Moreover, gene set variation analysis (GSVA) and univariate Cox regression were applied to filter prognostic signalling pathways. Additionally, significant DEIG and immune cells/pathways, and significant DEIG and pathways were co-analysed. Further, differential enriched pathways were identified by GSEA. In sum, a scientific hypothesis for recurrence LGG including TF, immune gene and immune cell/pathway was established. In our study, a total of 536 primary LGG samples, 2,498 immune genes and 318 TFs were acquired. Based on edgeR method, 2,164 DEGs, 2,498 DEIGs and 31 differentials expressed TFs were identified. A total of 106 DEIGs were integrated into multivariate prognostic model. Additionally, the AUC of the ROC curve was 0.860, and P value of Kaplan-Meier curve < 0.001. GATA6 (TF) and COL3A1 (DEIG) were selected (R = 0.900, P < 0.001, positive) as significant TF-immune gene links. Type II IFN response (P < 0.001) was the significant immune pathway. Propanoate metabolism (P < 0.001) was the significant KEGG pathway. We proposed that COL3A1 was positively regulated by GATA6, and by effecting type II IFN response and propanoate metabolism, COL3A1 involved in LGG recurrence.

Keywords: low-grade glioma; prognosis; propanoate metabolism; recurrence; type II IFN response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Brain Neoplasms / genetics
  • Brain Neoplasms / immunology
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / pathology
  • Collagen Type III / physiology*
  • Female
  • GATA6 Transcription Factor / physiology*
  • Gene Expression Regulation, Neoplastic*
  • Gene Regulatory Networks
  • Glioma / genetics
  • Glioma / immunology
  • Glioma / metabolism*
  • Glioma / pathology
  • Humans
  • Interferon alpha-2 / biosynthesis*
  • Interferon alpha-2 / genetics
  • Male
  • Metabolic Networks and Pathways / genetics
  • Metabolic Networks and Pathways / immunology
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / physiology*
  • Neoplasm Recurrence, Local / metabolism*
  • Neoplasm Recurrence, Local / pathology
  • Prognosis
  • Propionates / metabolism*
  • Proportional Hazards Models
  • Risk
  • Young Adult

Substances

  • Collagen Type III
  • GATA6 Transcription Factor
  • Interferon alpha-2
  • Neoplasm Proteins
  • Propionates