Huang Bi, Tian Li, Chen Zhaoran, Zhang Liang, Su Wenjun, Lu Tianyi, Yang Yanmin, Hui Rutai, Wang Xiaojian, Fan Xiaohan
State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Front Cardiovasc Med. 2021 Dec 23;8:743519. doi: 10.3389/fcvm.2021.743519. eCollection 2021.
Biomarker-assisted diagnosis of acute aortic dissection (AAD) is important for initiation of treatment and improved survival. However, identification of biomarkers for AAD in blood is a challenging task. The present study aims to find the potential AAD biomarkers using a transcriptomic strategy. Arrays based genome-wide gene expression profiling were performed using ascending aortic tissues which were collected from AAD patients and healthy donors. The differentially expressed genes were validated using quantitative reverse transcriptase PCR (qRT-PCR) and western blot. The plasma levels of a potential biomarker, angiopoietin 2 (ANGPT2) were determined in case-control cohort (77 AAD patients and 82 healthy controls) by enzyme linked immunosorbent assay. Receiver operating characteristic curve (ROC) was used to evaluate the diagnostic power of ANGPT2 for AAD. Transcriptome data demonstrated that a total of 18 genes were significantly up-regulated and 28 genes were significantly down-regulated among AAD tissues (foldchange>3.0, < 0.01). By bioinformatic analysis, we identified ANGPT2 as a candidate biomarker for blood-based detection of AAD. The qRT-PCR and protein expression demonstrated that ANGPT2 increased 2.4- and 4.2 folds, respectively in aortic tissue of AAD patients. Immunohistochemical staining demonstrated that ANGPT2 was markedly increased in intima of the aortic wall in AAD. Furthermore, ANGPT2 was significantly elevated in AAD patients as compared with controls (median 1625 vs. 383 pg/ml, < 1E-6). ROC curve analysis showed that ANGPT2 was highly predictive of a diagnosis of type A AAD (area under curve 0.93, < 1E-6). Sensitivity and specificity were 81 and 90%, respectively at the cutoff value of 833 pg/ml. In conclusion, ANGPT2 could be a promising biomarker for diagnosis of AAD; however, more studies are still needed to verify its specificity in diagnosing of AAD.
生物标志物辅助诊断急性主动脉夹层(AAD)对于启动治疗和提高生存率至关重要。然而,在血液中鉴定AAD的生物标志物是一项具有挑战性的任务。本研究旨在使用转录组学策略寻找潜在的AAD生物标志物。使用从AAD患者和健康供体收集的升主动脉组织进行基于阵列的全基因组基因表达谱分析。使用定量逆转录聚合酶链反应(qRT-PCR)和蛋白质免疫印迹法验证差异表达基因。通过酶联免疫吸附测定法在病例对照队列(77例AAD患者和82例健康对照)中测定潜在生物标志物血管生成素2(ANGPT2)的血浆水平。采用受试者工作特征曲线(ROC)评估ANGPT2对AAD的诊断能力。转录组数据表明,AAD组织中共有18个基因显著上调,28个基因显著下调(倍数变化>3.0,<0.01)。通过生物信息学分析,我们确定ANGPT2为基于血液检测AAD的候选生物标志物。qRT-PCR和蛋白质表达表明,AAD患者主动脉组织中ANGPT2分别增加了2.4倍和4.2倍。免疫组织化学染色表明,AAD患者主动脉壁内膜中ANGPT2明显增加。此外,与对照组相比,AAD患者中ANGPT2显著升高(中位数1625 vs. 383 pg/ml,<1E-6)。ROC曲线分析表明,ANGPT2对A型AAD诊断具有高度预测性(曲线下面积0.93,<1E-6)。在临界值833 pg/ml时,敏感性和特异性分别为81%和90%。总之,ANGPT2可能是AAD诊断的一个有前景的生物标志物;然而,仍需要更多研究来验证其在AAD诊断中的特异性。