Song Hongbin, Hu Zhonghui, Zhang Shiyu, Yang Lu, Feng Jindi, Lu Lu, Liu Yuehua, Wang Tao
Department of Dermatology, Peking Union Medical College Hospital, State Key Laboratory of Complex Severe and Rare Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases, Dongcheng District, Beijing, 100730, China.
Department of Dermatology, People's Hospital of Ningxia Hui Autonomous Region, Ningxia Medical University, Yinchuan, China.
Clin Proteomics. 2024 Aug 13;21(1):53. doi: 10.1186/s12014-024-09503-7.
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.
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有特异性（如红斑或斑块），它常被误诊为炎症性皮肤病（如特应性皮炎、银屑病和玫瑰糠疹），从而导致治疗延误。由于目前尚无用于MF早期检测和管理的有效生物标志物，本研究的目的是对尿液样本（作为一种非侵入性蛋白质来源）进行蛋白质组学分析，以鉴定可靠的MF生物标志物。
13例早期MF患者接受皮下注射干扰素α-2a联合光疗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者的进行比较。对差异表达的蛋白质进行基因本体论、京都基因与基因组百科全书和直系同源簇分析。为进行验证，通过酶联免疫吸附测定（ELISA）评估所选蛋白质的水平。
我们在未经治疗的MF患者与健康对照者之间鉴定出41种差异表达的蛋白质（11种过表达和30种低表达）。这些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患者尿液中丝氨酸蛋白酶抑制剂B5（Serpin B5）、表皮生长因子（EGF）和Ras同源基因家族成员A（RhoA）的水平显著低于健康对照者。然而，治疗6个月后，MF患者与健康对照者尿液中Serpin B5、EGF和RhoA的水平无显著差异。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。
本研究表明，尿液蛋白质组学是研究MF的一种有价值的工具，同时鉴定出了潜在的新生物标志物（Serpin B5、EGF和RhoA），可用于MF的诊断和管理。
