Department of Oncology-Pathology, Karolinska Institutet Solna, Stockholm, Sweden.
Division of Oncology and Pathology, Department of Clinical Sciences, Faculty of Medicine, Lund University, Uppsala, Sweden.
Pathobiology. 2018;85(4):211-219. doi: 10.1159/000486285. Epub 2018 Apr 4.
The aim of this study was to identify differences in proteome profiles of diffuse large B-cell lymphoma (DLBCL) of nongerminal center (non-GC) versus GC type in the search for new markers and drug targets.
Six DLBCL, with 3 repeats for each, were used for the initial study by proteomics: 3 non-GC and 3 GC DLBCL cases. For immunohistochemistry, tissue microarrays were made from 31 DLBCL samples: 16 non-GC de novo lymphomas and 15 GC cases (11 transformed from follicular lymphomas and 4 de novo GC lymphomas). Proteome profiling was performed by two-dimensional gel electrophoresis and MALDI-TOF mass spectrometry.
Ninety-one proteins were found differentially expressed in non-GC compared to GC type. The Cytoscape tool was used for systemic analysis of proteomics data, revealing 19 subnetworks representing functions affected in non-GC versus GC types of DLBCL.
A validation study of 3 selected proteins (BiP/Grp78, Hsp90, and cyclin B2) showed the enhanced expression in non-GC DLBCL, supporting the proteomics data.
本研究旨在通过蛋白质组学研究，确定非生发中心（non-GC）与生发中心（GC）弥漫性大 B 细胞淋巴瘤（DLBCL）之间的蛋白质组图谱差异，以寻找新的标记物和药物靶点。
采用蛋白质组学方法对 6 例 DLBCL 进行初始研究，每个类型重复 3 次：3 例非 GC 型和 3 例 GC 型 DLBCL。为进行免疫组织化学研究，从 31 例 DLBCL 样本中制作组织微阵列：16 例非 GC 初发性淋巴瘤和 15 例 GC 病例（11 例由滤泡性淋巴瘤转化而来，4 例为 GC 初发性淋巴瘤）。通过二维凝胶电泳和 MALDI-TOF 质谱进行蛋白质组分析。
与 GC 型相比，非 GC 型发现有 91 种蛋白质表达差异。使用 Cytoscape 工具对蛋白质组学数据进行系统分析，揭示了 19 个代表非 GC 与 GC 型 DLBCL 中受影响功能的子网。
对 3 种选定蛋白质（BiP/Grp78、Hsp90 和细胞周期蛋白 B2）的验证研究表明，非 GC DLBCL 中表达增强，支持蛋白质组学数据。
