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Abstract：
Hepatic complications are an acknowledged cause of mortality and morbidity among patients undergoing hematopoietic stem cell transplantation. In this study, we aimed to evaluate the potential role in the prediction of liver injury of five selected microRNAs (miRNAs)-miR-122-5p, miR-122-3p, miR-15b-5p, miR-99b-5p, and miR-125a-5p-in the setting of autologous hematopoietic stem cell transplantation (ASCT). A total of 66 patients were included in the study: 50 patients (75.8%) with multiple myeloma (MM) and 16 (24.2%) with lymphoma. Blood samples were collected after the administration of the conditioning regimen, on the day of transplant (day 0). The expression levels of selected miRNAs were quantified by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) using the miRCURY LNA miRNA Custom PCR Panels (QIAGEN). In a multivariate logistic regression analysis adjusted for age, sex, and the administered conditioning regimen, two miRNAs, hsa-miR-122-5p (odds ratio, OR 2.10, 95% confidence interval, CI: 1.29-3.42, p = 0.0029) and hsa-miR-125a-5p (OR 0.27, 95% CI: 0.11-0.71, p = 0.0079), were independent for hepatic toxicity occurrence during the 14 days after transplant. Our model in 10-fold cross-validation preserved its diagnostic potential with a receiver operating characteristics area under the curve (ROC AUC) of 0.75, 95% CI: 0.63-0.88 and at optimal cut-off reached 72.0% sensitivity and 74.4% specificity. An elevated serum level of miR-122-5p and decreased level of miR-125a-5p on day 0 are independent risk factors for hepatotoxicity in ASCT recipients, showing promise in accurately predicting post-ASCT complications. Identifying patients susceptible to complications has the potential to reduce procedure costs and optimize the selection of inpatient or outpatient procedures.
摘要：
在接受造血干细胞移植的患者中,肝脏并发症是公认的死亡和发病的原因。在这项研究中,我们的目的是评估五个选择的microRNAs（miRNAs）-miR-122-5p在预测肝损伤中的潜在作用，miR-122-3p,miR-15b-5p,miR-99b-5p,和miR-125a-5p-在自体造血干细胞移植（ASCT）的背景下。共纳入66例患者：50例（75.8%）多发性骨髓瘤（MM）患者和16例（24.2%）淋巴瘤患者。在施用调理方案后收集血样，移植当天（第0天）。使用miRCURYLNAmiRNA定制PCR面板(QIAGEN)通过逆转录-定量聚合酶链反应(RT-qPCR)定量选择的miRNA的表达水平。在调整年龄的多元逻辑回归分析中，性别,和施用的调理方案，两个miRNA,hsa-miR-122-5p(比值比，或2.10，95%置信区间，CI：1.29-3.42，p=0.0029）和hsa-miR-125a-5p（OR0.27，95％CI：0.11-0.71，p=0.0079），在移植后14天内独立于肝毒性发生。我们的模型在10倍交叉验证中保留了其诊断潜力，受试者工作特征曲线下面积（ROCAUC）为0.75，95％CI：0.63-0.88，在最佳截止处达到72.0％的灵敏度和74.4％的特异性。第0天血清miR-122-5p水平升高和miR-125a-5p水平降低是ASCT受者肝毒性的独立危险因素。在准确预测ASCT后并发症方面显示出希望。识别易受并发症影响的患者有可能降低手术成本并优化住院或门诊手术的选择。
