Diagnosis of thymic epithelial tumor subtypes by a quantitative proteomic approach
Diagnosis of thymic epithelial tumor subtypes by a quantitative proteomic approach
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通过定量蛋白质组学方法诊断胸腺上皮肿瘤亚型。
作者：
Zhao Ting;Wu Jie;Liu Xiaohui;Zhang Lei;Chen Gang;Lu Haojie
胸腺上皮肿瘤（TET）的组织学分型对于外科病理学家来说仍然是一个挑战，特别是当遇到主要集中在梭形细胞类型（包括A型、非典型A型（aA）、AB和B3）的临界病例时。采用同量异序标记相对和绝对定量（iTRAQ）标记结合二维液相色谱-串联质谱（2D-LC-MS/MS）对TcB进行了系统的蛋白质组学分析。总共分别鉴定和定量了6479和6305种蛋白质。经基因本体（GO）注释和免疫途径分析（IPA）后，通过组织芯片或多反应监测（MRM）定量验证6个差异表达蛋白。ABCE 1和CLIC 2有望成为胸腺癌诊断的候选生物标志物。与A型胸腺瘤相比，CHD 1 L在AB型和B型胸腺瘤中表达上调。CLIC 2和MAP 7在B1和B2型胸腺瘤中均呈阴性。SMAD 4在aA型胸腺瘤和TC中过表达。与其他亚型相比，CDC 42在B2型胸腺瘤中表达显著下调。发现六种新的候选生物标志物可用于区分TcB亚型。SMAD 4可能在aA型胸腺瘤和胸腺癌的发生、发展中发挥特异性作用。
The histological typing of thymic epithelial tumours (TETs) still remains a challenge for surgical pathologists, especially when encountering borderline cases mainly focused on spindle cell types (including type A, atypical type A (aA), AB, and B3). A systematic proteomics analysis of TETs was performed using isobaric tags for relative and absolute quantification (iTRAQ) labeling coupled with two-dimensional liquid chromatography-tandem mass spectrometry (2D-LC-MS/MS). In total, 6479 and 6305 proteins were identified and quantified, respectively. After Gene Ontology (GO) annotation and Ingenuity Pathway Analysis (IPA), six differentially expressed proteins were validated by tissue microarray or multiple reaction monitoring (MRM) quantification. ABCE1 and CLIC2 are promising to be diagnostic candidate biomarkers in thymic carcinomas (TCs). CHD1L was up-regulated in type AB and type B thymomas compared with type A thymoma. Both CLIC2 and MAP7 were negatively detected in type B1 and B2 thymomas. SMAD4 was overexpressed in type aA thymomas and TCs. CDC42 was significantly down-regulated in type B2 thymomas compared with other subtypes. Six novel candidate biomarkers were found to be useful in differentiating subtypes of TETs. SMAD4 may play a specific role in tumorigenesis and the development of aA thymomas and thymic carcinomas.