Pérez-Carrillo Lorena, Giménez-Escamilla Isaac, González-Torrent Irene, Delgado-Arija Marta, Sánchez-Lázaro Ignacio, García-Manzanares María, Martínez-Dolz Luis, Portolés Manuel, Tarazón Estefanía, Roselló-Lletí Esther
Clinical and Translational Research in Cardiology Unit, Health Research Institute Hospital La Fe (IISLaFe), Valencia, Spain.
CIBERCV, Madrid, Spain.
Biomark Res. 2024 May 12;12(1):49. doi: 10.1186/s40364-024-00590-0.
Long non-coding RNAs (lncRNAs) are closely implicated in biological processes and diseases with high inflammatory components. These molecules exhibit significant temporal and tissue specificity. However, the expression and function of lncRNAs have not been studied in patients after heart transplantation. Thus, we aimed to identify circulating lncRNAs in these patients and evaluate their diagnostic capacity as potential biomarkers for the non-invasive detection of acute cellular rejection (ACR). For them, we performed a transcriptomic study based on ncRNA-seq technology to detect lncRNAs in serum samples, matched to routine endomyocardial biopsies, from patients without rejection episode (0R, n = 12) and with mild (1R, n = 16) or moderate-severe (≥ 2R, n = 12) ACR. We identified 11,062 circulating lncRNAs in the serum of patients after heart transplantation. Moreover, 6 lncRNAs showed statistically significant expression when the different ACR grades were compared. Among them, AC008105.3, AC006525.1, AC011455.8, AL359220.1, and AC025279.1 had relevant diagnostic capacity for detection of ≥ 2R (AUC of 0.850 to 1.000) and 1R (AUC of 0.750 to 0.854) grades, along with high specificity and positive predictive values (≥ 83%). In addition, AL359220.1 and AC025279.1 were independent predictors for the presence of moderate-severe ACR (odds ratio = 31.132, p < 0.01 and C statistic = 0.939, p < 0.0001; odds ratio = 18.693, p < 0.05 and C statistic = 0.902, p < 0.001; respectively). In conclusion, we describe, for the first time, circulating lncRNAs after heart transplantation as potential candidates for non-invasive detection of ACR. AL359220.1 and AC025279.1 showed excellent diagnostic capability correlating with the severity episode and were strong independent predictors of rejection.
长链非编码RNA（lncRNAs）与具有高度炎症成分的生物过程和疾病密切相关。这些分子表现出显著的时间和组织特异性。然而，lncRNAs在心脏移植患者中的表达和功能尚未得到研究。因此，我们旨在鉴定这些患者体内的循环lncRNAs，并评估它们作为急性细胞排斥反应（ACR）非侵入性检测潜在生物标志物的诊断能力。为此，我们基于ncRNA测序技术进行了一项转录组学研究，以检测来自无排斥反应发作（0R，n = 12）、轻度（1R，n = 16）或中重度（≥2R，n = 12）ACR患者的血清样本中的lncRNAs，这些血清样本与常规心内膜心肌活检样本相匹配。我们在心脏移植患者的血清中鉴定出11,062种循环lncRNAs。此外，当比较不同ACR等级时，有6种lncRNAs表现出统计学上的显著表达。其中，AC008105.3、AC006525.1、AC011455.8、AL359220.1和AC025279.1对检测≥2R（曲线下面积为0.850至1.000）和1R（曲线下面积为0.750至0.854）等级具有相关诊断能力，同时具有高特异性和阳性预测值（≥83%）。此外，AL359220.1和AC025279.1是中重度ACR存在的独立预测因子（优势比分别为31.132，p < 0.01和C统计量 = 0.939，p < 0.0001；优势比为18.693，p < 0.05和C统计量 = 0.902，p < 0.001）。总之，我们首次描述了心脏移植后的循环lncRNAs作为ACR非侵入性检测的潜在候选物。AL359220.1和AC025279.1显示出与严重程度相关的出色诊断能力，并且是排斥反应的强有力独立预测因子。
