Jiang Zhibin, Hu Ping, Liu Jianxin, Wang Dianjun, Jin Longyu, Hong Chao
Department of Cardiothoracic Surgery, The Third Xiangya Hospital, Central South University, Changsha, Hunan, P.R. China.
Department of Cardiothoracic Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, P.R. China.
PLoS One. 2014 Jun 30;9(6):e100149. doi: 10.1371/journal.pone.0100149. eCollection 2014.
Postoperative myocardial infarction (PMI) is one of the most serious complications of cardiac surgeries. No preoperative biomarker is currently available for predicting PMI after cardiac surgeries. In the present study, we used a phage display peptide library to screen potential preoperative peptide biomarkers for predicting PMI after coronary artery bypass grafting (CABG) surgery. Twenty patients who developed PMI after CABG and 20 age-, sex-, and body mass index-matched patients without PMI after CABG were enrolled as a discovery cohort. Another 50 patients who developed PMI after CABG and 50 randomly selected patients without PMI after CABG were enrolled as a validation cohort to validate the potential peptide biomarkers identified in the discovery cohort. Fifty randomly selected healthy volunteers were also enrolled in the validation phase as a healthy control group. In the discovery/screening phase, 17 out of 20 randomly selected phage clones exhibited specific reaction with purified sera IgG from the PMI group, among which 11 came from the same phage clone with inserted peptide sequence GVIMVIAVSCVF (named PMI-1). In the validation phase, phage ELISA showed that serum IgG from 90% of patients in the PMI group had a positive reaction with PMI-1; in contrast, only 14% and 6% of patients in the non-PMI group and the healthy control group had a positive reaction with PMI-1, respectively. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of the PMI-1 phage clone to preoperatively identify patients who would develop PMI after CABG were 90.0%, 86.0%, 86.5, 89.5% and 88.0%, respectively. The absorbance value of the PMI-1 phage clone showed statistically significant correlation with the peak postoperative serum cardiac troponin I level (r = 0.349, p = 0.012) in the PMI group. In conclusion, we for the first time identified a mimic peptide (PMI-1) with high validity in preoperative prediction of PMI after CABG.
术后心肌梗死（PMI）是心脏手术最严重的并发症之一。目前尚无术前生物标志物可用于预测心脏手术后的PMI。在本研究中，我们使用噬菌体展示肽库筛选潜在的术前肽生物标志物，以预测冠状动脉旁路移植术（CABG）后的PMI。将20例CABG术后发生PMI的患者和20例年龄、性别及体重指数匹配的CABG术后未发生PMI的患者纳入发现队列。另外50例CABG术后发生PMI的患者和50例随机选择的CABG术后未发生PMI的患者作为验证队列，以验证在发现队列中鉴定出的潜在肽生物标志物。还将50例随机选择的健康志愿者纳入验证阶段作为健康对照组。在发现/筛选阶段，随机选择的20个噬菌体克隆中有17个与PMI组纯化的血清IgG发生特异性反应，其中11个来自同一噬菌体克隆，其插入的肽序列为GVIMVIAVSCVF（命名为PMI-1）。在验证阶段，噬菌体ELISA显示PMI组90%患者的血清IgG与PMI-1呈阳性反应；相比之下，非PMI组和健康对照组分别只有14%和6%的患者与PMI-1呈阳性反应。PMI-1噬菌体克隆术前识别CABG术后发生PMI患者的敏感性、特异性、阳性预测值、阴性预测值和准确性分别为90.0%、86.0%、86.5%、89.5%和88.0%。PMI组中PMI-1噬菌体克隆的吸光度值与术后血清心肌肌钙蛋白I峰值水平呈统计学显著相关（r = 0.349，p = 0.012）。总之我们首次鉴定出一种模拟肽（PMI-1），在术前预测CABG术后PMI方面具有较高的有效性。
