Alegre Estibaliz, Zubiri Leyre, Perez-Gracia Jose Luis, González-Cao María, Soria Lourdes, Martín-Algarra Salvador, González Alvaro
Laboratory of Biochemistry, University Clinic of Navarra, Spain.
Department of Medical Oncology, University Clinic of Navarra, Spain.
Clin Chim Acta. 2016 Feb 15;454:28-32. doi: 10.1016/j.cca.2015.12.031. Epub 2015 Dec 24.
Malignant melanoma is an aggressive cancer with an increasing incidence. Exosomes are actively secreted microvesicles, whose characteristics reflect those of the cell they are originated in. The aim of this study was to identify and evaluate the presence of the melanoma biomarkers MIA, S100B and tyrosinase-related protein 2 (TYRP2) in exosomes and their potential clinical utility.
Serum samples were obtained from stage IV melanoma patients, melanoma-free patients and healthy controls. Exosomes were precipitated and TYRP2, MIA and S100B concentrations were quantified in serum, exosomes, and exosome-free serum.
Both MIA and S100B were detected in exosomes and correlated significantly with serum concentrations (S100B: r=0.968; MIA: r=0.799; p<0.001). MIA and S100B concentrations in exosomes were significantly higher in melanoma patients than in healthy controls and disease-free patients. However, TYRP2 concentrations in exosomes did not differ between these three groups. ROC curves analysis rendered AUCs for MIA of 0.883 (p<0.01) and of 0.840 for S100B (p<0.01). Patients with exosome MIA concentration higher than 2.5 μg/L showed shorter median survival related to those with lower level (4 versus 11 months; p<0.05).
MIA and S100B can be detected in exosomes from melanoma patients and their quantification presents diagnostic and prognostic utility.
恶性黑色素瘤是一种侵袭性癌症，发病率呈上升趋势。外泌体是细胞主动分泌的微囊泡，其特性反映了产生它们的细胞的特性。本研究的目的是鉴定和评估黑色素瘤生物标志物黑色素瘤抑制因子（MIA）、S100B蛋白和酪氨酸酶相关蛋白2（TYRP2）在外泌体中的存在情况及其潜在的临床应用价值。
采集IV期黑色素瘤患者、无黑色素瘤患者和健康对照者的血清样本。沉淀外泌体，并对血清、外泌体和无外泌体血清中的TYRP2、MIA和S100B浓度进行定量分析。
在外泌体中检测到MIA和S100B，且它们与血清浓度显著相关（S100B：r = 0.968；MIA：r = 0.799；p < 0.001）。黑色素瘤患者外泌体中的MIA和S100B浓度显著高于健康对照者和无病患者。然而，这三组之间外泌体中的TYRP2浓度没有差异。ROC曲线分析得出MIA的曲线下面积（AUC）为0.883（p < 0.01），S100B的AUC为0.840（p < 0.01）。外泌体MIA浓度高于2.5μg/L的患者中位生存期短于浓度较低的患者（4个月对11个月；p < 0.05）。
在黑色素瘤患者的外泌体中可检测到MIA和S100B，对它们进行定量分析具有诊断和预后价值。
