title: Differential proteomics analysis of low- and high-grade of astrocytoma using iTRAQ quantification.
abstract: Astrocytoma is one of the most common types of brain tumor, which is histologically and clinically classified into four grades (I-IV): I (pilocytic astrocytoma), II (diffuse astrocytoma), III (anaplastic astrocytoma), and IV (glioblastoma multiforme). A higher grade astrocytoma represents a worse prognosis and is more aggressive. In this study, we compared the differential proteome profile of astrocytoma from grades I to IV. The protein samples from clinical specimens of grades I, II, III, and IV astrocytoma were analyzed by two-dimensional liquid chromatography-tandem mass spectrometry and isobaric tags for relative and absolute quantitation and quantification. A total of 2,190 proteins were identified. Compared to grade I astrocytoma, 173 (12.4%), 304 (14%), and 462 (21.2%) proteins were aberrantly expressed in grades II, III, and IV, respectively. By bioinformatics analysis, the cell proliferation, invasion, and angiogenesis-related pathways increase from low- to high-grade of astrocytoma. Five differentially expressed proteins were validated by Western blot. Within them, matrix metalloproteinase-9 and metalloproteinase inhibitor 1 were upregulated in glioblastoma multiforme group; whereas fibulin-2 and -5 were downregulated in grade II/III/IV astrocytoma, and the negative expression was significantly associated with advanced clinical stage. Functional analysis showed that both fibulin-2 and -5 may exert an antitumor effect by inhibiting cell proliferation, in vitro migration/invasion in glioma cells. New molecular biomarkers are likely to be used for accurate classification of astrocytoma and likely to be the target for drug development.
authors.affiliation: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing.
authors.forename: Tong
authors.initials: T
authors.lastname: Ren
authors.affiliation: Department of Spinal Cord Injury, Institute of Orthopedics and Traumatology of Chinese PLA, General Hospital of Jinan Military Area Command, Jinan.
authors.forename: Shide
authors.initials: S
authors.lastname: Lin
authors.affiliation: State Key Laboratory of Medical Neurobiology, Shanghai Medical College, Fudan University, Shanghai.
authors.forename: Zhongfeng
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, General Hospital of Chinese People's Liberation Army of China, Beijing, People's Republic of China.
authors.forename: Aijia
authors.initials: A
authors.lastname: Shang
keywords: Fibulin-2; Fibulin-5; astrocytoma; bio-markers; brain tumor; clinical grades; glioma