Biomarker discovery: A proteomic approach for brain cancer profiling
Biomarker discovery: A proteomic approach for brain cancer profiling
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DOI：
10.1111/j.1349-7006.2007.00374.x
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发表时间：
2007-02-01
期刊：
影响因子：
5.7
通讯作者：
James, Peter
中科院分区：
文献类型：
--
作者：
Khalil, Ashraf A.;James, Peter
星形细胞瘤、间变性星形细胞瘤和胶质母细胞瘤形式的胶质瘤是人类最常见的脑肿瘤。早期发现这些癌症对于成功治疗至关重要。蛋白质组学有望发现用于早期检测和诊断的生物标志物和肿瘤标志物。本研究采用差异凝胶电泳技术结合基质辅助激光解吸/电离-飞行时间和液相色谱-串联质谱技术研究人脑肿瘤蛋白质组的肿瘤特异性变化。包含不同诊断组（非肿瘤、I级、II级、III级和IV级）的五十个人脑组织与每个凝胶上的内部合并样本一起运行两份。自动挑选感兴趣的蛋白质，凝胶内消化和质谱指纹。211个蛋白质点被成功鉴定，并被分解成91个独特的蛋白质。据我们所知，这91种独特蛋白质中约有20种以前未被报道为在人类脑癌中差异表达。与非肿瘤组织相比，多形性胶质母细胞瘤中Alb蛋白、过氧化物酶氧还蛋白4和SH 3结构域结合的富含谷氨酸样蛋白3上调。然而，与非肿瘤组织相比，在多形性胶质母细胞瘤中，果糖二磷酸醛缩酶C、肌酸激酶、B链二氢硫辛酰脱氢酶、烯醇化酶2、富马酸水合酶、HSP 60、乳酰谷胱甘肽裂解酶、Lucine氨基肽酶、Mu-crystallin同系物、NADH-UO 24、神经丝三联体L蛋白、septin 2、stathmin和空泡ATP合成酶亚单位E表达下调。这些差异表达的蛋白质提供了新的信息之间存在的差异正常脑和胶质瘤，因此可能被证明是有用的分子指标的诊断或预后价值。
Gliomas in the form of astrocytomas, anaplastic astrocytomas and glioblastomas are the most common brain tumors in humans. Early detection of these cancers is crucial for successful treatment. Proteomics promises the discovery of biomarkers and tumor markers for early detection and diagnosis. In the current study, a differential gel electrophoresis technology coupled with matrix-assisted laser desorption/ionization-time of flight and liquid chromatography-tandem mass spectroscopy was used to investigate tumor-specific changes in the proteome of human brain cancer. Fifty human brain tissues comprising varying diagnostic groups (non-tumor, grade I, grade II, grade III and grade IV) were run in duplicate together with an internal pool sample on each gel. The proteins of interest were automatically picked, in-gel digested and mass spectrometry fingerprinted. Two hundred and eleven protein spots were identified successfully and were collapsed into 91 unique proteins. Approximately 20 of those 91 unique proteins had, to our knowledge, not been reported previously as differentially expressed in human brain cancer. Alb protein, peroxiredoxin 4 and SH3 domain-binding glutamic acid-rich-like protein 3 were upregulated in glioblastoma multiform versus non-tumor tissues. However, aldolase C fructose-biphosphate, creatine kinase, B chain dihydrolipoyl dehydrogenase, enolase 2, fumarate hydratase, HSP60, lactoylglutathione lyase, lucine aminopeptidase, Mu-crystallin homolog, NADH-UO 24, neurofilament triplet L protein, septin 2, stathmin and vacuolar ATP synthase subunit E were downregulated in glioblastoma multiform compared with non-tumor tissues. These differentially expressed proteins provided novel information on the differences existing between normal brain and gliomas, and thus might prove to be useful molecular indicators of diagnostic or prognostic value.