Proteomic Identification Of Differential Markers For Oligodendrogliomas And Astrocytomas

Part Ⅰ IntroductionThis part is to introduce the related background of the subject, and review the previous applications of proteomic profiling in neurosurgical diseases.Part Ⅱ Proteomic identification of differential markers for oligodendrogliomas and astrocytomas:Identification and comparison of proteomic patterns in oligodendrogliomas and astrocytomas; validation of glutamine synthetase expression in various grades of oligodendrogliomas, astrocytomas and oligoastrocytomas; and the investigation of glutaming synthetase expression in the differentiation of astrocyte progenitor cells.Background and Objective. Astrocytomas and oligodendrogliomas are primary central nervous system (CNS) tumors that remain a challenge to differentiate histologically due to morphological variability, lack of reliable differential diagnostic markers and the existence of oligoastrocytomas. To identify proteins that are differentially expressed between astrocytomas and oligodendrogliomas, we analyzed the proteomic expression patterns and identified uniquely expressed proteins in these neoplasms.Materials and Methods. Proteomes of astrocytomas and oligodendrogliomas were analyzed using2-dimensional gel electrophoresis followed by computerized gel analysis to detect differentially expressed proteins. Proteins were identified by high-performance liquid chromatography accompanied by tandem mass spectrometry. Glutamine synthetase (GS) was targeted as a candidate marker and was detected by western blot and immunohistochemistry in different grades of astrocytomas, oligoastrocytomas and oligodendrogliomas. To determine the role of the differentially expressed proteins in astrocytes, undifferentiated glial cell cultures were treated with dibutryl-cAMP.Results. Two-dimensional gel electrophoresis revealed that glutamine synthetase was one of the seven proteins which are differentially expressed in astrocytomas and oligodendrogliomas. The increased expression of glutamine synthetase in astrocytomas compared to oligodendrogliomas was confirmed by Western blot and immunohistochemical analyses. While GS expression was demonstrated across all grades of astrocytomas (grade II to IV,5for each;15tumors) and oligoastrocytomas (grade II to III,2for each), it was expressed in only1(6%) oligodendroglioma (16tumors,13for grade II and3for grade III). Treatment of undifferentiated glial cell cultures with dibutryl-cAMP resulted in astrocyte differentiation that was associated with increased levels of glial fibrillary acidic protein (GFAP) and glutamine synthetase.Conclusions. These data indicate that (1)7different proteins are expressed in oligodendrogliomas and astrocytomas,(2)glutamine synthetase expression can be used to distinguish astrocytic from oligodendroglial tumors, and (3) glutamine synthetase may play a role in the differentiation of progenitor astrocyte cells and in the pathogenesis of astrocytomas.