Uridine phosphorylase 1 is a novel immune-related target and predicts worse survival in brain glioma

Cancer Med. 2020 Aug;9(16):5940-5947. doi: 10.1002/cam4.3251. Epub 2020 Jun 24.

Abstract

Uridine phosphorylase 1 (UPP1) has been reported as an oncogene in several malignancies. In glioma, the role of UPP1 remains unclear. This study was performed to explore its role in glioma at transcriptional level. Totally, 998 glioma patients with clinical data were enrolled, including 301 mRNA microarray data from Chinese Glioma Genome Atlas (CGGA) dataset and 697 RNAseq data from The Cancer Genome Atlas (TCGA) dataset. Statistical analysis was performed with R language. UPP1 expression level was positively correlated with WHO grade of glioma. UPP1 was significantly upregulated in mesenchymal subtype and could serve as a potential biomarker for this subtype. Based on most correlated genes of UPP1, Gene ontology analysis revealed that UPP1 was profoundly associated with immune and inflammatory response. Gene Sets Variation Analysis was further performed and showed that UPP1 was particularly correlated with MHC-II and LCK, which were mainly associated with activities of antigen-presenting cells and T cells. Moreover, UPP1 was found to be synergistic with various immune checkpoint members, especially with PD1 pathway and B7-H3. Finally, Kaplan-Meier curves revealed that higher UPP1 indicated significantly shorter survival for glioma patients. Taken together, UPP1 played an oncogenic role in glioma via suppressing tumor-related immune response.

Keywords: UPP1; glioma; immune response; prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Brain Neoplasms / enzymology*
  • Brain Neoplasms / mortality*
  • Brain Neoplasms / pathology
  • Glioma / enzymology*
  • Glioma / mortality*
  • Glioma / pathology
  • Humans
  • Immune Checkpoint Proteins / metabolism
  • Isocitrate Dehydrogenase / genetics
  • Kaplan-Meier Estimate
  • Prognosis
  • Up-Regulation
  • Uridine Phosphorylase / genetics
  • Uridine Phosphorylase / metabolism*

Substances

  • Biomarkers, Tumor
  • Immune Checkpoint Proteins
  • Isocitrate Dehydrogenase
  • UPP1 protein, human
  • Uridine Phosphorylase