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首页> 外文期刊>Modern Pathology >Novel prognostic markers revealed by a proteomic approach separating benign from malignant insulinomas
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Novel prognostic markers revealed by a proteomic approach separating benign from malignant insulinomas

机译：蛋白质组学方法将良性与恶性胰岛素瘤分离的新预后标志物

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The prognosis of pancreatic neuroendocrine tumors is related to size, histology and proliferation rate. However, this stratification needs to be refined further. We conducted a proteome study on insulinomas, a well-defined pancreatic neuroendocrine tumor entity, in order to identify proteins that can be used as biomarkers for malignancy. Based on a long follow-up, insulinomas were divided into those with metastases (malignant) and those without (benign). Microdissected cells from six benign and six malignant insulinomas were subjected to a procedure combining fluorescence dye saturation labeling with high-resolution two-dimensional gel electrophoresis. Differentially expressed proteins were identified using nano liquid chromatography–electrospray ionization/multi-stage mass spectrometry and validated by immunohistochemistry on tissue microarrays containing 62 insulinomas. Sixteen differentially regulated proteins were identified among 3000 protein spots. Immunohistochemical validation revealed that aldehyde dehydrogenase 1A1 and voltage-dependent anion-selective channel protein 1 showed significantly stronger expression in malignant insulinomas than in benign insulinomas, whereas tumor protein D52 (TPD52) binding protein was expressed less strongly in malignant insulinomas than in benign insulinomas. Using multivariate analysis, low TPD52 expression was identified as a strong independent prognostic factor for both recurrence-free and overall disease-related survival.
机译：胰腺神经内分泌肿瘤的预后与大小，组织学和增殖率有关。但是，这种分层需要进一步完善。我们对胰岛素瘤（一种定义明确的胰腺神经内分泌肿瘤实体）进行了蛋白质组学研究，以鉴定可用作恶性生物标志物的蛋白质。根据长期随访，将胰岛素瘤分为转移灶（恶性）和无转移灶（良性）。对来自六个良性和六个恶性胰岛素瘤的显微解剖细胞进行结合荧光染料饱和度标记和高分辨率二维凝胶电泳的程序。使用纳米液相色谱-电喷雾电离/多级质谱法鉴定差异表达的蛋白质，并通过免疫组织化学对包含62个胰岛素瘤的组织微阵列进行验证。在3000个蛋白斑点中鉴定出16种差异调节蛋白。免疫组织化学验证显示，醛脱氢酶1A1和电压依赖性阴离子选择性通道蛋白1在恶性胰岛素瘤中的表达明显强于良性胰岛素瘤，而肿瘤蛋白D52（TPD52）结合蛋白在恶性胰岛素瘤中的表达不如在良性胰岛素瘤中强。使用多变量分析，TPD52的低表达被确定为无复发和总体疾病相关生存的强大独立预后因素。

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