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胸腺瘤的蛋白质组学特征

Proteomic Signatures of Thymomas.

作者信息

Wang Linan, Branson Owen E, Shilo Konstantin, Hitchcock Charles L, Freitas Michael A

机构信息

Department of Cancer Biology and Genetics, The Ohio State University Wexner Medical Center, Columbus, OH, United States of America.

The Ohio State University Comprehensive Cancer Center, Columbus, OH, United States of America.

出版信息

PLoS One. 2016 Nov 10;11(11):e0166494. doi: 10.1371/journal.pone.0166494. eCollection 2016.

Abstract

Based on the histological features and outcome, the current WHO classification separates thymomas into A, AB, B1, B2 and B3 subtypes. It is hypothesized that the type A thymomas are derived from the thymic medulla while the type B thymomas are derived from the cortex. Due to occasional histological overlap between the tumor subtypes creating difficulties in their separation, the aim of this study was to provide their proteomic characterization and identify potential immunohistochemical markers aiding in tissue diagnosis. Pair-wise comparison of neoplastic and normal thymus by liquid chromatography tandem mass spectrometry (LC-MS/MS) of formalin fixed paraffin embedded tissue revealed 61 proteins differentially expressed in thymomas compared to normal tissue. Hierarchical clustering showed distinct segregation of subtypes AB, B1 and B2 from that of A and B3. Most notably, desmoyokin, a protein that is encoded by the AHNAK gene, was associated with type A thymomas and medulla of normal thymus, by LC-MS/MS and immunohistochemistry. In this global proteomic characterization of the thymoma, several proteins unique to different thymic compartments and thymoma subtypes were identified. Among differentially expressed proteins, desmoyokin is a marker specific for thymic medulla and is potentially promising immunohistochemical marker in separation of type A and B3 thymomas.

摘要

根据组织学特征和预后情况,世界卫生组织(WHO)目前的分类将胸腺瘤分为A、AB、B1、B2和B3亚型。据推测,A型胸腺瘤起源于胸腺髓质,而B型胸腺瘤起源于皮质。由于肿瘤亚型之间偶尔存在组织学重叠,给它们的区分带来困难,本研究的目的是对其进行蛋白质组学表征,并鉴定有助于组织诊断的潜在免疫组化标志物。通过对福尔马林固定石蜡包埋组织进行液相色谱串联质谱分析(LC-MS/MS),对肿瘤性胸腺和正常胸腺进行成对比较,结果显示与正常组织相比,胸腺瘤中有61种蛋白质表达存在差异。层次聚类显示AB、B1和B2亚型与A和B3亚型明显分离。最值得注意的是,由AHNAK基因编码的一种蛋白质——桥粒肌动蛋白,通过LC-MS/MS和免疫组化分析,与A型胸腺瘤和正常胸腺的髓质相关。在本次胸腺瘤的整体蛋白质组学表征中,鉴定出了几种不同胸腺区室和胸腺瘤亚型特有的蛋白质。在差异表达的蛋白质中,桥粒肌动蛋白是胸腺髓质的特异性标志物,在区分A型和B3型胸腺瘤方面可能是一种很有前景的免疫组化标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e8d/5104371/67e422f2c0a5/pone.0166494.g001.jpg

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