Glioma proteomics: Status and perspectives

Norlux Neuro-Oncology Laboratory, Department of Oncology, Centre de Recherche Public de la Santé (CRP-Santé), Luxembourg, Luxembourg.
Journal of proteomics (Impact Factor: 3.89). 03/2010; 73(10):1823-38. DOI: 10.1016/j.jprot.2010.03.007
Source: PubMed


High grade gliomas are the most common brain tumors in adults and their malignant nature makes them the fourth biggest cause of cancer death. Major efforts in neuro-oncology research are needed to reach similar progress in treatment efficacy as that achieved for other cancers in recent years. In addition to the urgent need to identify novel effective drug targets against malignant gliomas, the search for glioma biomarkers and grade specific protein signatures will provide a much needed contribution to diagnosis, prognosis, treatment decision and assessment of treatment response. Over the past years glioma proteomics has been attempted at different levels, including proteome analysis of patient biopsies and bodily fluids, of glioma cell lines and animal models. Here we provide an extensive review of the outcome of these studies in terms of protein identifications (protein numbers and regulated proteins), with an emphasis on the methods used and the limitations of the studies with regard to biomarker discovery. This is followed by a perspective on novel technologies and on the potential future contribution of proteomics in a broad sense to understanding glioma biology.

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    • "A large number of review articles have appeared in the past several years, offering excellent overviews and perspectives on novel proteomic applications in cancer. Many reviews focused on different cancer types, such as breast cancer,1–4 pancreatic cancer,5,6 ovarian cancer,7–9 colorectal cancer,10,11 and glioma.12–14 Others have focused on sample types or subcellular components, such as tissue,15–17 serum,18–20 and secretome.21–23 "
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    ABSTRACT: Proteomic approaches are continuing to make headways in cancer research by helping to elucidate complex signaling networks that underlie tumorigenesis and disease progression. This review describes recent advances made in the proteomic discovery of drug targets for therapeutic development. A variety of technical and methodological advances are overviewed with a critical assessment of challenges and potentials. A number of potential drug targets, such as baculoviral inhibitor of apoptosis protein repeat-containing protein 6, macrophage inhibitory cytokine 1, phosphoglycerate mutase 1, prohibitin 1, fascin, and pyruvate kinase isozyme 2 were identified in the proteomic analysis of drug-resistant cancer cells, drug action, and differential disease state tissues. Future directions for proteomics-based target identification and validation to be more translation efficient are also discussed.
    Drug Design, Development and Therapy 10/2013; 7:1259-1271. DOI:10.2147/DDDT.S52216 · 3.03 Impact Factor
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    • "Even following gross total resection and optimal adjuvant treatment, recurrence is extremely common, mainly from the margin of the resection cavity [3] [4] [5]. GB is a very heterogenous groups of tumors [6], involving different zones; both genomic [7] [8] and proteomic [9] [10] [11] approaches have been used to study these tumors. These analyses led to the identification of different markers, allowing the characterization of different subtypes of GBs and tumoral mechanisms, and may serve as a basis for the development of new therapies focused on the molecular, genetic and proteomic particularities of GB. "
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    ABSTRACT: Unlabelled: Glioblastoma (GB) is the most frequent and aggressive tumor of the central nervous system. There is currently growing interest in proteomic studies of GB, particularly with the aim of identifying new prognostic or therapeutic response markers. However, comparisons between different proteomic analyses of GB have revealed few common differentiated proteins. The types of control samples used to identify such proteins may in part explain the different results obtained. We therefore tried to determine which control samples would be most suitable for GB proteomic studies. We used an isotope-coded protein labeling (ICPL) method followed by mass spectrometry to reveal and compare the protein patterns of two commonly used types of control sample: GB peritumoral brain zone samples (PBZ) from six patients and epilepsy surgery brain samples (EB) pooled from three patients. The data obtained were processed using AMEN software for network analysis. We identified 197 non-redundant proteins and 35 of them were differentially expressed. Among these 35 differentially expressed proteins, six were over-expressed in PBZ and 29 in EB, showing different proteomic patterns between the two samples. Surprisingly, EB appeared to display a tumoral-like expression pattern in comparison to PBZ. In our opinion, PBZ may be more appropriate control sample for GB proteomic analysis. Biological significance: This manuscript describes an original study in which we used an isotope-coded protein labeling method followed by mass spectrometry to identify and compare the protein patterns in two types of sample commonly used as control for glioblastoma (GB) proteomic analysis: peritumoral brain zone and brain samples obtained during surgery for epilepsy. The choice of control samples is critical for identifying new prognostic and/or diagnostic markers in GB.
    Journal of proteomics 05/2013; 85. DOI:10.1016/j.jprot.2013.04.031 · 3.89 Impact Factor
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    • "More recently, a proteome profile has also been compared between normal brain tissue and different grades of glioma tissue. Recent reviews by Whittle et al. [14] and Niclou et al. [15] nicely summarized the current status of glioma proteomics and its clinical applications. The glioma proteome has been previously analyzed using patient samples (glioma tissue or body fluid such as serum), cultured glioma cell lines, or animal models in an effort to enhance our understanding of glioma biology as well as to search for protein biomarkers that contribute to a better diagnosis and prognosis of glioma and to a better evaluation of drug responses to glioma [16]. "
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    ABSTRACT: Malignant glioma is the most common and destructive form of primary brain tumor. Along with surgery and radiation, chemotherapy remains as the major treatment modality. The emergence of drug resistance, however, often leads to a therapeutic failure in the treatment of glioma, precluding long-term survival of the patients. A proteomic approach has recently been adapted for the mechanistic analysis of glioma drug resistance. The proteomic analysis of drug-resistant glioma led to the discovery of novel biomarkers that can be used for the prognosis of glioma as well as for monitoring the drug response or resistance of glioma. These proteomics-based biomarkers can also be a druggable target that one can exploit for successful glioma chemotherapy. In this review, recent reports on proteomic analysis of glioma from the perspective of chemoresistance are discussed with a focus on the proteome profiles of glioma cells that are resistant to the alkylating agent, 1, 3-bis (2-chloroethyl)-1-nitrosourea (BCNU), as a prime example. Among numerous proteins that were up- or down-regulated in drug-resistant glioma cells, lipocalin 2 (LCN2) and integrin β3 (ITGB3) were identified as key proteins that determine the survival and death of glioma cells. LCN2, ITGB3, and other proteins identified by proteomic analysis could be utilized to overcome glioma chemoresistance.
    DNA research: an international journal for rapid publication of reports on genes and genomes 03/2012; 10(1):72-9. DOI:10.2174/157015912799362733 · 3.05 Impact Factor
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