The molecular pathology of diffuse large B cell lymphoma (DLBCL) has been extensively studied. Among DLBCL subtypes, the prognosis of CD5-positive DLBCL is worse than that of CD5-negative DLBCL, considering the central nervous system relapse and poor response to R-CHOP therapy. However, the molecular mechanisms underlying the tumorigenesis and progression of CD5-positive DLBCL remain unknown. To identify molecular markers that can be targeted for treating DLBCL, a proteomic study was performed using liquid chromatography-mass spectrometry with chemically pretreated formalin-fixed paraffin-embedded specimens from CD5-positive (n = 5) and CD5-negative DLBCL patients (n = 6). Twenty-one proteins showed significant downregulation in CD5-positive DLBCL compared to CD5-negative DLBCL. Principal component analysis of protein expression profiling in CD5-positive and CD5-negative DLBCL revealed that DNAJB1, DDX3X, and BTK, which is one of the B cell phenotypic proteins, were the most significantly downregulated proteins and served as biomarkers that distinguished both groups. Additionally, a set of immunoglobulins, including IgG4, exhibited significant downregulation. Immunohistochemistry analysis for BTK demonstrated reduced staining in CD5-positive DLBCL compared to CD5-negative DLBCL. In conclusion, DNAJB1 and DDX3X, BTK, and a set of immunoglobulins are promising biomarkers. Probably, the suppression of BCR signaling is the unique phenotype of CD5-positive DLBCL. This formalin-fixed paraffin-embedded (FFPE)-based profiling may help to develop novel therapeutic molecularly targeted drugs for treating DLBCL.

中文翻译：

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CD5 阳性弥漫性大 B 细胞淋巴瘤 FFPE 组织的蛋白质组分析显示 DDX3X、DNAJB1 和 B 细胞受体信号通路蛋白（包括 BTK 和免疫球蛋白）下调

弥漫性大 B 细胞淋巴瘤 (DLBCL) 的分子病理学已得到广泛研究。在DLBCL亚型中，考虑到中枢神经系统复发和对R-CHOP治疗反应不佳，CD5阳性DLBCL的预后比CD5阴性DLBCL差。然而，CD5阳性DLBCL肿瘤发生和进展的分子机制仍不清楚。为了确定可用于治疗 DLBCL 的分子标志物，使用液相色谱-质谱法对来自 CD5 阳性 (n = 5) 和 CD5 阴性 DLBCL 患者 (n = 5) 的经化学预处理的福尔马林固定石蜡包埋标本进行了蛋白质组学研究。 = 6）。与 CD5 阴性 DLBCL 相比，21 种蛋白质在 CD5 阳性 DLBCL 中表现出显着下调。CD5 阳性和 CD5 阴性 DLBCL 中蛋白质表达谱的主成分分析显示，DNAJB1、DDX3X 和 BTK（B 细胞表型蛋白之一）是下调最显着的蛋白，可作为区分这两个群体的生物标志物。此外，包括 IgG4 在内的一组免疫球蛋白表现出显着的下调。BTK 的免疫组织化学分析表明，与 CD5 阴性 DLBCL 相比，CD5 阳性 DLBCL 的染色减少。总之，DNAJB1 和 DDX3X、BTK 以及一组免疫球蛋白是有前途的生物标志物。BCR 信号传导的抑制可能是 CD5 阳性 DLBCL 的独特表型。这种基于福尔马林固定石蜡包埋 (FFPE) 的分析可能有助于开发用于治疗 DLBCL 的新型治疗性分子靶向药物。