Department of NanoEngineering, University of California, San Diego, USA.
Research Unit of Hypertension and Cardiovascular Epidemiology, Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium.
Sci Rep. 2017 Jun 30;7(1):4419. doi: 10.1038/s41598-017-04801-7.
Bone marrow mononuclear cell (BM-MNC) therapy in ST-elevation acute myocardial infarction (STEMI) has no biological inclusion criteria. Here, we analyzed 63 biomarkers and cytokines in baseline plasma samples from 77 STEMI patients treated with BM-MNCs in the TIME and Late-TIME trials as well as 61 STEMI patients treated with placebo. Response to cell therapy was defined by changes in left ventricular ejection fraction, systolic/diastolic volumes, and wall motion indexes. We investigated the clinical value of circulating proteins in outcome prediction using significance testing, partial least squares discriminant analysis, and receiver operating characteristic (ROC) analysis. Responders had higher biomarker levels (76-94% elevated) than non-responders. Several biomarkers had values that differed significantly (P < 0.05) between responders and non-responders including stem cell factor, platelet-derived growth factor, and interleukin-15. We then used these lead candidates for ROC analysis and found multiple biomarkers with values areas under the curve >0.70 including interleukin 15. These biomarkers were not involved in the placebo-treated subjects suggesting that they may have predictive power. We conclude that plasma profiling after STEMI may help identify patients with a greater likelihood of response to cell-based treatment. Prospective trials are needed to assess the predictive value of the circulating biomarkers.
骨髓单个核细胞（BM-MNC）治疗 ST 段抬高型急性心肌梗死（STEMI）没有生物学纳入标准。在这里，我们分析了 TIME 和 Late-TIME 试验中 77 例接受 BM-MNC 治疗的 STEMI 患者和 61 例接受安慰剂治疗的 STEMI 患者的基线血浆样本中的 63 种生物标志物和细胞因子。细胞治疗的反应通过左心室射血分数、收缩/舒张容积和壁运动指数的变化来定义。我们使用显著性检验、偏最小二乘判别分析和接收者操作特征（ROC）分析来研究循环蛋白在预后预测中的临床价值。反应者的生物标志物水平（76-94%升高）高于无反应者。一些生物标志物在反应者和无反应者之间的差异具有统计学意义（P<0.05），包括干细胞因子、血小板衍生生长因子和白细胞介素-15。然后，我们使用这些候选标志物进行 ROC 分析，发现多个具有曲线下面积>0.70 的生物标志物，包括白细胞介素 15。这些生物标志物未参与安慰剂治疗的患者，表明它们可能具有预测能力。我们得出结论，STEMI 后血浆分析可能有助于识别对基于细胞的治疗反应更大的患者。需要前瞻性试验来评估循环生物标志物的预测价值。
