Gal-1 Expression Analysis in the GLIOCAT Multicenter Study: Role as a Prognostic Factor and an Immune-Suppressive Biomarker

Cells. 2023 Mar 8;12(6):843. doi: 10.3390/cells12060843.

Abstract

Glioblastoma (GBM) is the most frequent primary malignant brain tumor and has a dismal prognosis. Unfortunately, despite the recent revolution of immune checkpoint inhibitors in many solid tumors, these have not shown a benefit in overall survival in GBM patients. Therefore, new potential treatment targets as well as diagnostic, prognostic, and/or predictive biomarkers are needed to improve outcomes in this population. The β-galactoside binding protein Galectin-1 (Gal-1) is a protein with a wide range of pro-tumor functions such as proliferation, invasion, angiogenesis, and immune suppression. Here, we evaluated Gal-1 expression by immunohistochemistry in a homogenously treated cohort of GBM (the GLIOCAT project) and correlated its expression with clinical and molecular data. We observed that Gal-1 is a negative prognostic factor in GBM. Interestingly, we observed higher levels of Gal-1 expression in the mesenchymal/classical subtypes compared to the less aggressive proneural subtype. We also observed a Gal-1 expression correlation with immune suppressive signatures of CD4 T-cells and macrophages, as well as with several GBM established biomarkers, including SHC1, PD-L1, PAX2, MEOX2, YKL-40, TCIRG1, YWHAG, OLIG2, SOX2, Ki-67, and SOX11. Moreover, Gal-1 levels were significantly lower in grade 4 IDH-1 mutant astrocytomas, which have a better prognosis. Our results confirm the role of Gal-1 as a prognostic factor and also suggest its value as an immune-suppressive biomarker in GBM.

Keywords: Galectin-1; IDH-1; glioblastoma; immune-suppression; mesenchymal molecular subtype; prognostic factor.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 14-3-3 Proteins / metabolism
  • Astrocytoma* / metabolism
  • Biomarkers
  • Galectin 1 / genetics
  • Galectin 1 / metabolism
  • Glioblastoma* / diagnosis
  • Glioblastoma* / genetics
  • Glioblastoma* / metabolism
  • Humans
  • Prognosis
  • Vacuolar Proton-Translocating ATPases* / metabolism

Substances

  • Galectin 1
  • Biomarkers
  • TCIRG1 protein, human
  • Vacuolar Proton-Translocating ATPases
  • YWHAG protein, human
  • 14-3-3 Proteins

Grants and funding

This work was supported by grants from the Fundació LaMarató TV3 (665/C/2013; http://www.ccma.cat/tv3/marato/projectes-financats/2012/231/) to CB, FA and NI, and from the Spanish Ministry of Science and Innovation (MICINN)/Instituto de Salud Carlos III (ISCIII)-FEDER (PI20/00625) and the “Generalitat de Catalunya” (2017/SGR/225) to PN. Noelia Vilariño is supported by a Rio Hortega scholarship (CM19/00245). AE-C is funded by ISCIII/MINECO (PT17/0009/0019) and co-funded by FEDER.