RUNX1/CD44 axis regulates the proliferation, migration, and immunotherapy of gliomas: A single-cell sequencing analysis

Front Immunol. 2023 Jan 26:14:1086280. doi: 10.3389/fimmu.2023.1086280. eCollection 2023.

Abstract

Background: Glioma is one of the most common, primary, and lethal adult brain tumors because of its extreme aggressiveness and poor prognosis. Several recent studies relevant to the immune function of CD44, a transmembrane glycoprotein as a significant hyaluronic acid receptor, have achieved great success, revealing the critical role of CD44 in immune infiltration in gliomas. The overexpression of CD44 has been verified to correlate with cancer aggressiveness and migration, while the clinical and immune features of CD44 expression have not yet been thoroughly characterized in gliomas.

Methods: Molecular and clinical data of glioma collected from publicly available genomic databases were analyzed.

Results: CD44 was up-expressed in malignant gliomas, notably in the 1p/19q non-codeletion cases, isocitrate dehydrogenase (IDH) wild-type, and mesenchymal subtypes in GBM samples. CD44 expression level strongly correlates with stromal and immune cells, mainly infiltrating the glioma microenvironment by single-cell sequencing analysis. Meanwhile, CD44 can be a promising biomarker in predicting immunotherapy responses and mediating the expression of PD-L1. Finally, RUNX1/CD44 axis could promote the proliferation and migration of gliomas.

Conclusions: Therefore, CD44 was responsible for glioma growth and progression. It could potentially lead to a novel target for glioma immunotherapy or a prognostic biomarker.

Keywords: CD44; PD-L1; RUNX1; glioma; immunotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers
  • Cell Proliferation / genetics
  • Chromosome Aberrations
  • Core Binding Factor Alpha 2 Subunit* / genetics
  • Glioma* / genetics
  • Glioma* / pathology
  • Glioma* / therapy
  • Humans
  • Hyaluronan Receptors / genetics
  • Mutation
  • Tumor Microenvironment / genetics

Substances

  • Core Binding Factor Alpha 2 Subunit
  • Biomarkers
  • CD44 protein, human
  • Hyaluronan Receptors
  • RUNX1 protein, human

Grants and funding

This study was supported by the Science Foundation of Chongqing (cstc2019jcyj-msxmX0231) and the Chongqing Scientific and Health Joint Medical Research Project (2020GDRC021).