背景:真菌病(MF)是最常见的皮肤T细胞淋巴瘤类型。由于MF的早期临床表现是非特异性的(例如,红斑或斑块),它经常被误诊为炎性皮肤病(例如,特应性皮炎,牛皮癣,和玫瑰糠疹),导致治疗延迟。由于MF的早期检测和管理没有有效的生物标志物,本研究的目的是对尿液样本(作为非侵入性蛋白质来源)进行蛋白质组学分析,以鉴定可靠的MF生物标志物.
方法:13例早期MF患者皮下注射干扰素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进行比较。将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,和直系同源群分析。对于验证,通过酶联免疫吸附试验(ELISA)评估所选蛋白质的水平.
结果: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种过表达和30种过表达)。蛋白质主要富集在粘着灶中,内吞作用,和PI3K-Akt,磷脂酶D,MAPK,和钙信号通路。ELISA结果证实尿中SerpinB5、表皮生长因子(EGF)、未经治疗的MF患者的Ras同源基因家族成员A(RhoA)显着低于健康对照组。经过6个月的治疗,然而,尿中SerpinB5、EGF、MF患者和健康对照组之间的RhoA。SerpinB5、EGF、和RhoA分别为0.817、0.900和0.933。
结论:这项研究表明,尿液蛋白质组学是研究MF的有价值的工具,以及确定的潜在新生物标志物(SerpinB5,EGF,和RhoA),可用于其诊断和管理。
BACKGROUND: 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.
METHODS: 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).
RESULTS: 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.
CONCLUSIONS: 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.