弥漫性大B细胞淋巴瘤（DLBCL）的分子病理学已经得到了广泛研究。在DLBCL亚型中，CD5阳性DLBCL的预后比CD5阴性DLBCL差，考虑到中枢神经系统复发和对R-CHOP疗法的反应不佳。然而，CD5阳性DLBCL肿瘤发生和进展的分子机制仍然未知。为了鉴定可以用于治疗DLBCL的分子标志物，我们使用液相色谱-质谱技术对来自CD5阳性（n = 5）和CD5阴性DLBCL患者（n = 6）的化学预处理的福尔马林固定石蜡切片标本进行了蛋白质组学研究。与CD5阴性DLBCL相比，CD5阳性DLBCL显示出21种蛋白质的明显下调。在CD5阳性和CD5阴性DLBCL中的蛋白质表达谱的主成分分析表明，DNAJB1、DDX3X和BTK（一种B细胞表型蛋白）是最显著下调的蛋白质，并作为区分两个组的生物标志物。此外，一组免疫球蛋白，包括IgG4，显示明显下调。通过对BTK的免疫组化分析，我们发现CD5阳性DLBCL的染色显著减少。总之，DNAJB1、DDX3X、BTK和一组免疫球蛋白是有希望的生物标志物。可能，BCR信号抑制是CD5阳性DLBCL的独特表型。这种基于福尔马林固定石蜡切片（FFPE）的分析有助于开发用于治疗DLBCL的新型靶向分子药物。© 2023. BioMed Central Ltd., Springer Nature的一部分。

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.© 2023. BioMed Central Ltd., part of Springer Nature.