A Cell-Surface Membrane Protein Signature for Glioblastoma

Dhimankrishna Ghosh, Cory C. Funk, Juan Caballero, Nameeta Shah, Katherine Rouleau, John C. Earls, Liliana Soroceanu, Greg Foltz, Charles S. Cobbs, Nathan D. Price, Leroy Hood

Research output: Contribution to journalArticlepeer-review

Abstract

We present a systems strategy that facilitated the development of a molecular signature for glioblastoma (GBM), composed of 33 cell-surface transmembrane proteins. This molecular signature, GBMSig, was developed through the integration of cell-surface proteomics and transcriptomics from patient tumors in the REMBRANDT (n = 228) and TCGA datasets (n = 547) and can separate GBM patients from control individuals with a Matthew's correlation coefficient value of 0.87 in a lock-down test. Functionally, 17/33 GBMSig proteins are associated with transforming growth factor β signaling pathways, including CD47, SLC16A1, HMOX1, and MRC2. Knockdown of these genes impaired GBM invasion, reflecting their role in disease-perturbed changes in GBM. ELISA assays for a subset of GBMSig (CD44, VCAM1, HMOX1, and BIGH3) on 84 plasma specimens from multiple clinical sites revealed a high degree of separation of GBM patients from healthy control individuals (area under the curve is 0.98 in receiver operating characteristic). In addition, a classifier based on these four proteins differentiated the blood of pre- and post-tumor resections, demonstrating potential clinical value as biomarkers.

Original languageEnglish (US)
Pages (from-to)516-529.e7
JournalCell Systems
Volume4
Issue number5
DOIs
StatePublished - May 24 2017
Externally publishedYes

Keywords

  • GBM
  • GBMSig
  • cell-surface proteins
  • invasion

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology
  • Cell Biology

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