Extracellular Matrix Proteome Remodeling in Human Glioblastoma and Medulloblastoma

J Proteome Res. 2021 Oct 1;20(10):4693-4707. doi: 10.1021/acs.jproteome.1c00251. Epub 2021 Sep 17.

Abstract

Medulloblastomas (MBs) and glioblastomas (GBMs) are high-incidence central nervous system tumors. Different origin sites and changes in the tissue microenvironment have been associated with the onset and progression. Here, we describe differences between the extracellular matrix (ECM) signatures of these tumors. We compared the proteomic profiles of MB and GBM decellularized tumor samples between each other and their normal decellularized brain site counterparts. Our analysis revealed that 19, 28, and 11 ECM proteins were differentially expressed in MBs, GBMs, and in both MBs and GBMs, respectively. Next, we validated key findings by using a protein tissue array with 53 MB and 55 GBM cases and evaluated the clinical relevance of the identified differentially expressed proteins through their analysis on publicly available datasets, 763 MB samples from the GSE50161 and GSE85217 studies, and 115 GBM samples from RNAseq-TCGA. We report a shift toward a denser fibrillary ECM as well as a clear alteration in the glycoprotein signature, which influences the tumor pathophysiology. MS data have been submitted to the PRIDE repository, project accession: PXD023350.

Keywords: decellularization; extracellular matrix; glioblastoma; mass spectrometry; medulloblastoma; proteome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain Neoplasms* / genetics
  • Extracellular Matrix* / pathology
  • Glioblastoma* / genetics
  • Humans
  • Medulloblastoma* / genetics
  • Proteome / genetics
  • Proteomics
  • Tumor Microenvironment

Substances

  • Proteome