title: A Cell-Surface Membrane Protein Signature for Glioblastoma.
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.
authors.affiliation: Institute for Systems Biology, Seattle, WA 98109, USA.
authors.forename: Dhimankrishna
authors.initials: D
authors.lastname: Ghosh
authors.affiliation: Institute for Systems Biology, Seattle, WA 98109, USA.
authors.forename: Cory C
authors.initials: CC
authors.lastname: Funk
authors.affiliation: Institute for Systems Biology, Seattle, WA 98109, USA.
authors.forename: Juan
authors.initials: J
authors.lastname: Caballero
authors.affiliation: The Ben and Catherine Ivy Center for Advanced Brain Tumor Treatment, Swedish Neuroscience Institute, Seattle, WA 98122, USA.
authors.forename: Nameeta
authors.initials: N
authors.lastname: Shah
authors.affiliation: Institute for Systems Biology, Seattle, WA 98109, USA.
authors.forename: Katherine
authors.initials: K
authors.lastname: Rouleau
authors.affiliation: Institute for Systems Biology, Seattle, WA 98109, USA; Department of Computer Science and Engineering, University of Washington, Seattle, WA 98195, USA.
authors.forename: John C
authors.initials: JC
authors.lastname: Earls
authors.affiliation: California Pacific Medical Center Research Institute, San Francisco, CA 94107, USA.
authors.forename: Liliana
authors.initials: L
authors.lastname: Soroceanu
authors.affiliation: The Ben and Catherine Ivy Center for Advanced Brain Tumor Treatment, Swedish Neuroscience Institute, Seattle, WA 98122, USA.
authors.forename: Greg
authors.initials: G
authors.lastname: Foltz
authors.affiliation: The Ben and Catherine Ivy Center for Advanced Brain Tumor Treatment, Swedish Neuroscience Institute, Seattle, WA 98122, USA.
authors.forename: Charles S
authors.initials: CS
authors.lastname: Cobbs
authors.affiliation: Institute for Systems Biology, Seattle, WA 98109, USA; Department of Computer Science and Engineering, University of Washington, Seattle, WA 98195, USA.
authors.forename: Nathan D
authors.initials: ND
authors.lastname: Price
authors.affiliation: Institute for Systems Biology, Seattle, WA 98109, USA. Electronic address: lhood@systemsbiology.org.
authors.forename: Leroy
authors.initials: L
authors.lastname: Hood
mesh_terms: D014408:Biomarkers, Tumor; D001932:Brain Neoplasms / Q000235:genetics; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D049109:Cell Proliferation; D019295:Computational Biology / Q000379:methods; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D040901:Proteomics / Q000379:methods; D049490:Systems Biology / Q000379:methods; D059467:Transcriptome / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D008565:Membrane Proteins; D016212:Transforming Growth Factor beta
keywords: GBM; GBMSig; cell-surface proteins; invasion