蕈样肉芽肿 (MF) 是最常见的皮肤 T 细胞淋巴瘤类型。由于 MF 的早期临床表现不具特异性（如红斑或斑块），常被误诊为炎症性皮肤病（如特应性皮炎、牛皮癣、玫瑰糠疹），从而延误治疗。由于没有有效的生物标志物用于 MF 的早期检测和管理，本研究的目的是对尿液样本（作为非侵入性蛋白质来源）进行蛋白质组分析，以确定可靠的 MF 生物标志物。 13 名早期患有 MF 的患者MF期皮下注射干扰素α-2a并结合光疗6个月。通过液相色谱-串联质谱法将早期 MF 患者治疗前后的尿液蛋白质组与健康对照进行比较。对差异表达的蛋白质进行基因本体论、京都基因和基因组百科全书以及直系同源群簇分析。为了进行验证，通过酶联免疫吸附测定 (ELISA) 评估了所选蛋白质的水平。我们在未经治疗的 MF 患者和健康对照受试者之间鉴定了 41 种差异表达的蛋白质（11 种过表达，30 种表达不足）。蛋白质主要富集于粘着斑、内吞作用以及 PI3K-Akt、磷脂酶 D、MAPK 和钙信号通路。 ELISA结果证实，未经治疗的MF患者尿液中Serpin B5、表皮生长因子（EGF）和Ras同源基因家族成员A（RhoA）的水平显着低于健康对照。然而，治疗 6 个月后，MF 患者和健康对照受试者尿液中 Serpin B5、EGF 和 RhoA 的水平没有显着差异。 Serpin B5、EGF 和 RhoA 的受试者工作特征曲线下面积值分别为 0.817、0.900 和 0.933。这项研究表明，尿液蛋白质组学是研究 MF 的一个有价值的工具，并确定了潜在的新生物标志物（Serpin B5、EGF 和 RhoA），可用于其诊断和管理。© 2024。作者。

Mycosis fungoides (MF) is the most common type of cutaneous T cell lymphoma. As the early clinical manifestations of MF are non-specific (e.g., erythema or plaques), it is often misdiagnosed as inflammatory skin conditions (e.g., atopic dermatitis, psoriasis, and pityriasis rosea), resulting in delayed treatment. As there are no effective biological markers for the early detection and management of MF, the aim of the present study was to perform a proteomic analysis of urine samples (as a non-invasive protein source) to identify reliable MF biomarkers.Thirteen patients with early-stage MF were administered a subcutaneous injection of interferon α-2a in combination with phototherapy for 6 months. The urine proteome of patients with early-stage MF before and after treatment was compared against that of healthy controls by liquid chromatography-tandem mass spectrometry. The differentially expressed proteins were subjected to Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and Clusters of Orthologous Groups analyses. For validation, the levels of the selected proteins were evaluated by enzyme-linked immunosorbent assay (ELISA).We identified 41 differentially expressed proteins (11 overexpressed and 30 underexpressed) between untreated MF patients and healthy control subjects. The proteins were mainly enriched in focal adhesion, endocytosis, and the PI3K-Akt, phospholipase D, MAPK, and calcium signaling pathways. The ELISA results confirmed that the urine levels of Serpin B5, epidermal growth factor (EGF), and Ras homologous gene family member A (RhoA) of untreated MF patients were significantly lower than those of healthy controls. After 6 months of treatment, however, there was no significant difference in the urine levels of Serpin B5, EGF, and RhoA between MF patients and healthy control subjects. The area under the receiver operating characteristic curve values for Serpin B5, EGF, and RhoA were 0.817, 0.900, and 0.933, respectively.This study showed that urine proteomics represents a valuable tool for the study of MF, as well as identified potential new biomarkers (Serpin B5, EGF, and RhoA), which could be used in its diagnosis and management.© 2024. The Author(s).