Lin Zenan, Süsskind Daniela
University Eye Hospital, Center for Ophthalmology, University of Tübingen, 72076 Tübingen, Germany.
Cancers (Basel). 2021 May 18;13(10):2464. doi: 10.3390/cancers13102464.
Blood-based B-cell activating factor (BAFF), growth differentiation factor-15 (GDF-15) and osteopontin (OPN) have been identified to be promising biomarkers for the metastases of uveal melanoma (UM). This study intended to assess their kinetics and to evaluate their significance as a three-marker panel. A group of 36 UM patients with and 137 patients without metastases were included in the study. Their plasma OPN levels were measured by ELISA; serum BAFF and GDF-15 levels were determined with a Luminex MAGPIX system. Receiver operating characteristic (ROC) analysis was performed to calculate the cutoff values of the three markers for identifying the patients with metastases. The ability to identify patients with metastases was compared between the single markers and the combination as a three-marker panel. By using the Student's -test, we also investigated the kinetic changes of the levels of BAFF, GDF-15 and OPN across six periods (i.e., 0-6 months, 6-12 months, 12-18 months, 18-24 months, >24 months and post-metastasis) before the imaging diagnosis of metastases. By maximizing the Youden's index, the serum GDF-15 level of 1209 pg/mL and the plasma OPN level of 92 ng/mL were identified to have the best performance for distinguishing the metastatic patients from non-metastatic patients. The three-marker panel offered a better performance in distinguishing patients with metastases, with an area under the curve of 0.802, than any single biomarker. Increasing trends of the levels of three biomarkers were observed in the two-year period before the imaging diagnosis of metastases. The combined panel of BAFF, GDF-15 and OPN might be a utilizable implementation for the detection of UM metastases. In the bioinformatics study with two external datasets, the high expression of gene and in primary UM tissues was identified to be associated with poor overall survival rates. As the current work is a single-center retrospective study, more well-designed prospective investigations employing larger cohorts are urgently needed to validate our findings.
基于血液的B细胞活化因子（BAFF）、生长分化因子-15（GDF-15）和骨桥蛋白（OPN）已被确定为葡萄膜黑色素瘤（UM）转移的有前景的生物标志物。本研究旨在评估它们的动力学，并评估它们作为一个三标志物组合的意义。该研究纳入了36例有转移的UM患者和137例无转移的患者。通过酶联免疫吸附测定（ELISA）测量他们的血浆OPN水平；用Luminex MAGPIX系统测定血清BAFF和GDF-15水平。进行受试者操作特征（ROC）分析以计算这三种标志物用于识别有转移患者的临界值。比较了单个标志物与作为三标志物组合的识别有转移患者的能力。通过使用学生t检验，我们还研究了在转移的影像学诊断之前六个时期（即0 - 6个月、6 - 12个月、12 - 18个月、18 - 24个月、>24个月和转移后）BAFF、GDF-15和OPN水平的动力学变化。通过最大化约登指数，确定血清GDF-15水平为1209 pg/mL和血浆OPN水平为92 ng/mL在区分转移患者与非转移患者方面具有最佳性能。与任何单个生物标志物相比，三标志物组合在区分有转移患者方面表现更好，曲线下面积为0.802。在转移的影像学诊断前的两年期间观察到三种生物标志物水平呈上升趋势。BAFF、GDF-15和OPN的联合组合可能是检测UM转移的一种可利用的方法。在对两个外部数据集的生物信息学研究中，原发性UM组织中基因和的高表达被确定与较差的总生存率相关。由于当前工作是一项单中心回顾性研究，迫切需要更多设计良好的前瞻性研究，采用更大的队列来验证我们的发现。
