title: iTRAQ-based quantitative proteomic analysis for identification of oligodendroglioma biomarkers related with loss of heterozygosity on chromosomal arm 1p.
abstract: The oligodendroglioma (OG) type of glial cell tumors accounts for 2-5% of primary brain neoplasms and 4-15% of gliomas diagnosed worldwide. Allelic losses on 1p, or on 1p and 19q, correlate with chemotherapy response and good prognosis in OG patients; however, the underlying mechanisms are not yet clearly defined. Therefore, we utilized a quantitative proteomics strategy that combined 8-plex isobaric tags for relative and absolute quantitation (iTRAQ) labeling and two-dimensional liquid chromatography-tandem mass spectrometry (2D-LC/MS/MS) to identify molecular signatures, reveal mechanisms, and develop predictive markers of OG patients with 1p loss of heterozygosity (LOH). An initial screening of four OG patients with 1p LOH and four without were identified, and 449 differentially expressed proteins were quantified, 13 of which were significantly different between the two groups. Analysis of the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway suggested that 1p LOH may affect the actin network in OG. The differential expression of four of the 13 candidates (UBA1, ubiquitin-like modifier activating enzyme 1; ATP6V1E1, ATPase, H+ transporting, lysosomal 31 kDa, V1 subunit E1; MAP2, microtubule-associated protein 2; and HMGB1, high-mobility group protein B1) was validated in 39 additional OG samples using immunohistochemistry. Decision tree modeling indicated that MAP2 expression is a powerful predictor of 1p LOH. Our results not only demonstrate the utility of iTRAQ-based high-throughput quantitative proteomic analysis in glioma research, but also provide novel markers that may help to reveal the mechanisms of 1p LOH-associated chemosensitivity, and to design diagnostic and prognostic assays and therapeutics for OG.
authors.affiliation: Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai 200040, China.
authors.forename: Liu-song
authors.initials: LS
authors.lastname: Yang
authors.forename: Xiao-en
authors.initials: XE
authors.lastname: Xu
authors.forename: Xiu-ping
authors.initials: XP
authors.lastname: Liu
authors.forename: Hong
authors.initials: H
authors.lastname: Jin
authors.forename: Zhong-qing
authors.initials: ZQ
authors.lastname: Chen
authors.forename: Xiao-hui
authors.initials: XH
authors.lastname: Liu
authors.forename: Yin
authors.initials: Y
authors.lastname: Wang
authors.forename: Feng-ping
authors.initials: FP
authors.lastname: Huang
authors.forename: Qian
authors.initials: Q
authors.lastname: Shi
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D001932:Brain Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002878:Chromosomes, Human, Pair 1; D002888:Chromosomes, Human, Pair 19; D005260:Female; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009837:Oligodendroglioma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D040901:Proteomics / Q000379:methods
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins