Thanigaimani Shivshankar, Iyer Vikram, Bingley John, Browne Daniel, Phie James, Doolan Denise, Golledge Jonathan
Queensland Research Centre for Peripheral Vascular Disease, College of Medicine and Dentistry, James Cook University, Townsville, Queensland, Australia; Centre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns and Townsville, Queensland, Australia.
Queensland Research Centre for Peripheral Vascular Disease, College of Medicine and Dentistry, James Cook University, Townsville, Queensland, Australia; Centre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns and Townsville, Queensland, Australia; Department of Vascular Surgery, Royal Melbourne Hospital, Parkville, Victoria, Australia.
Eur J Vasc Endovasc Surg. 2023 Apr;65(4):573-581. doi: 10.1016/j.ejvs.2022.12.028. Epub 2022 Dec 31.
This study aimed to examine the association between serum microRNAs (miRNAs) and diagnosis and growth of abdominal aortic aneurysm (AAA), and to test their diagnostic and prognostic value.
The expression levels of 800 miRNA tags were assessed in 108 patients with AAA, 12 age and sex matched healthy controls (HCs), and 12 patients with peripheral artery disease (PAD) using NanoString technology. Findings were assessed in an independent sample of 66 patients with AAA and 29 age and sex matched HCs by reverse transcriptase polymerase chain reaction. AAA growth was assessed by a median of three (interquartile range [IQR] 2, 3) repeat ultrasound scans over a median follow up of 1.1 (IQR 1.0, 2.0) years. The association between the miRNA and AAA diagnosis and growth was examined by regression and linear mixed effects analyses. The diagnostic and prognostic potential of the miRNAs were examined using area under the receiver operator characteristic curve (AUC), net re-classification index (NRI), and Cox hazard analyses.
In comparison with HCs, a model combining clinical risk factors, let-7b-5p and miR-548n had an AUC of 98.0% (95% confidence interval [CI] 95.6 - 100.0; p = .003) for diagnosing AAA, which was a significant improvement over clinical risk factors alone (NRI 1.74; 95% CI 1.61 - 1.87; p < .001). Compared with PAD, a model combining clinical risk factors and miR-548n had an AUC of 99.6% (95% CI 98.9 - 100.0, p = .037) for diagnosing AAA, which was a significant improvement over clinical risk factors alone (NRI 1.79, 95% CI 1.68 - 1.91; p < .001). In the longitudinal cohort, none of the miRNAs were able to predict the likelihood of reaching surgical threshold diameter better than clinical risk factors alone.
Serum let-7b-5p and miR548n significantly improved the ability to diagnose AAA. None of the miRNAs had independent prognosis value in predicting AAA growth.
本研究旨在探讨血清微小RNA（miRNA）与腹主动脉瘤（AAA）诊断及生长之间的关联，并检验其诊断和预后价值。
使用NanoString技术评估了108例AAA患者、12例年龄和性别匹配的健康对照（HC）以及12例外周动脉疾病（PAD）患者中800个miRNA标签的表达水平。通过逆转录聚合酶链反应在66例AAA患者和29例年龄和性别匹配的HC组成的独立样本中评估研究结果。通过在中位随访1.1（四分位间距[IQR]1.0，2.0）年期间进行的中位三次（IQR 2，3）重复超声扫描评估AAA生长情况。通过回归分析和线性混合效应分析检验miRNA与AAA诊断及生长之间的关联。使用受试者操作特征曲线下面积（AUC）、净重新分类指数（NRI）和Cox风险分析检验miRNA的诊断和预后潜力。
与HC相比，一个结合临床风险因素、let-7b-5p和miR-548n的模型诊断AAA的AUC为98.0%（95%置信区间[CI]95.6 - 100.0；p = .003），与仅使用临床风险因素相比有显著改善（NRI 1.74；95% CI 1.61 - 1.87；p < .001）。与PAD相比，一个结合临床风险因素和miR-548n的模型诊断AAA的AUC为99.6%（95% CI 98.9 - 100.0，p = .037），与仅使用临床风险因素相比有显著改善（NRI 1.79，95% CI 1.68 - 1.91；p < .001）。在纵向队列中，没有一个miRNA能够比仅使用临床风险因素更好地预测达到手术阈值直径的可能性。
血清let-7b-5p和miR548n显著提高了诊断AAA的能力。没有一个miRNA在预测AAA生长方面具有独立的预后价值。
