Clinical and Translational Research in Cardiology Unit, Health Research Institute Hospital La Fe (IIS La Fe), Valencia, Spain.
Centro de Investigación Biomédica en Red en Enfermedades Cardiovasculares, Madrid, Spain.
Transplantation. 2023 Sep 1;107(9):2064-2072. doi: 10.1097/TP.0000000000004622. Epub 2023 Aug 21.
There is a dire need for specific, noninvasive biomarkers that can accurately detect cardiac acute cellular rejection (ACR) early. Previously, we described miR-144-3p as an excellent candidate for detecting grade ≥2R ACR. Now, we investigated the combination of miR-144-3p with miR-652-3p, other differentially expressed serum miRNA we previously described, to improve diagnostic accuracy mainly in mild rejection to avoid reaching severe stages.
We selected miR-652-3p from a preliminary RNA-seq study to be validated by reverse transcription-quantitative polymerase chain reaction on 212 consecutive serum samples from transplantation recipients undergoing routine endomyocardial biopsies to subsequently combine them with miR-144-3p results and investigate their diagnostic capability.
We confirmed the miR-652-3p overexpression (P < 0.0001) and its capability to discriminate between patients with and without ACR of any grade (P < 0.0001). The combined serum levels of miR-144-3p and miR-652-3p were significantly higher in patients with rejection regardless of posttransplantation time (P < 0.0001). This combination resulted in a diagnostic efficacy for 1R (area under the curve = 0.794) and ≥2R (area under the curve = 0.892; P < 0.0001) that was superior to each biomarker alone. Furthermore, it was a strong independent predictor of ACR for 1R (odds ratio of 10.950; P < 0.0001) and ≥2R (odds ratio of 14.289; P < 0.01).
We demonstrated that an appropriate combination of blood-based biomarkers could exhibit greater efficiency for cardiac rejection diagnosis. The combined detection of abnormal expression of miR-144-3p and miR-652-3p in the serum of ACR patients can improve the diagnostic sensitivity of rejection at an early stage and contribute to increasing the diagnostic accuracy, mainly in the lower rejection grades.
非常需要特异性、非侵入性的生物标志物，以便早期准确地检测心脏急性细胞排斥反应（ACR）。此前，我们将 miR-144-3p 描述为检测≥2R ACR 的优秀候选物。现在，我们研究了 miR-144-3p 与 miR-652-3p 的组合，miR-652-3p 是我们之前描述的其他差异表达的血清 miRNA 之一，以提高诊断准确性，主要是在轻度排斥反应中，以避免达到严重阶段。
我们从初步的 RNA-seq 研究中选择 miR-652-3p，通过逆转录定量聚合酶链反应（qRT-PCR）在 212 例连续接受常规心内膜心肌活检的移植受者的血清样本中进行验证，随后将其与 miR-144-3p 结果相结合，并研究其诊断能力。
我们证实了 miR-652-3p 的过表达（P<0.0001）及其区分任何等级 ACR 患者与非 ACR 患者的能力（P<0.0001）。无论移植后时间如何，排斥反应患者的血清 miR-144-3p 和 miR-652-3p 联合水平均显著升高（P<0.0001）。该组合对 1R（曲线下面积[AUC] = 0.794）和≥2R（AUC = 0.892；P<0.0001）的诊断效能均优于单独使用每种生物标志物。此外，它是 1R（优势比[OR]为 10.950；P<0.0001）和≥2R（OR 为 14.289；P<0.01）的 ACR 的强独立预测因子。
我们证明了血液生物标志物的适当组合可以提高心脏排斥反应诊断的效率。ACR 患者血清中 miR-144-3p 和 miR-652-3p 异常表达的联合检测可以提高早期排斥反应的诊断敏感性，有助于提高诊断准确性，特别是在较低的排斥等级。
