CS-25MOLECULAR SUBCLASSIFICATION OF GLIOBLASTOMA BASED ON THE ABSOLUTE QUANTITATIVE PROTEOMICS

Glioblastoma (GBM) has been classified into molecular subtypes with the advent of large-scale gene expression studies. The purpose of this study is to attempt to classify GBM subtypes based on the molecular profile determined by absolute quantitative proteomics and to investigate its clinical significance. The absolute protein expression levels of 13 species of receptor tyrosine kinases (RTKs) in 33 adult GBM surgical specimens were measured by the mass spectrometer which was set up to run a multi-channel reaction monitoring. For each tumor, we ascertained information on patient age, gender, IDH1 mutation, methylation status of MGMT promoter, progression-free survival (PFS) and overall survival (OS). Eight RTK proteins (EGFR, ERBB2, PDGFRα, PDGFRβ, VEGFR1, CD33, CD37, c-kit) were successfully quantified, whereas 5 protein levels were below detection limit. Large individual differences were observed in protein expression levels of each RTK. The highest mean expression level was detected for EGFR. GBMs in our study harbored mutually exclusive dominant expression of three RTKs; EGFR, ERBB2 and PDGFRα. Therefore, we propose a subclassification of GBM with respect to the dominant expression of these proteins; EGFR (n = 20), ERBB2 (n = 7) and PDGFRα (n = 6). The clinical characteristics of each group (EGFR, ERBB2, PDGFRα) are as follows: average age, (61.9, 58.4, 56.7 years old), gender (male/female, 15/5, 4/3, 6/0), IDH1 (wild/mutant, 18/2, 6/1, 6/0), MGMT promoter (methylated/unmethylated, 8/12, 3/4, 4/2), the median progression-free survival (PFS) (7.6, 10.0, 8.6 months), the median overall survival (OS) (13.7, 21.1, 13.8 months). PFS and OS tended to be longer in ERBB2 group in comparison with EGFR and PDGFRα group. Molecular subclassification of GBM based on the absolute quantitative proteomics reflects the clinical behavior and might have clinical significance.