Laminin Subunit Alpha-4 and Osteopontin Are Glioblastoma-Selective Secreted Proteins That Are Increased in the Cerebrospinal Fluid of Glioblastoma Patients.

Abstract

Glioblastoma (GBM) is the most common and aggressive brain tumor in adults. The purpose of the present study was to identify GBM cell-selective secreted proteins by analyzing conditioned media (CM) from GBM, breast, and colon cancer cell lines using sequential window acquisition of all theoretical spectra-mass spectrometry (SWATH-MS) and targeted proteomics. We identified 2371 proteins in the CM from GBM and the other cancer cell lines. Among the proteins identified, 15 showed significantly higher expression in the CM from GBM cell lines than in those from other cancer cell lines. These GBM-selective secreted proteins were further quantified in the cerebrospinal fluid (CSF) from patients with GBM. Laminin subunit alpha-4 (LAMA4) and osteopontin (OPN) had increased expression levels in the CSF from GBM patients compared to those from non-brain tumor patients. In addition, the areas under the curves in a receiver operating characteristic analysis of LAMA4 and OPN were greater than 0.9, allowing for discrimination of GBM patients from non-brain tumor patients. The CSF levels of LAMA4 and OPN were also significantly correlated with the GBM tumor volume. These results suggest that LAMA4 and OPN are secreted from GBM cells into the CSF and appear to be candidates as diagnostic markers and therapeutic targets for GBM.