Identification of plasma tRNA-derived small RNA i-tRF-15:31-Lys-CTT-1 as a biomarker for diagnosis and prognosis of pulmonary arterial hypertension

IF 5.6 3区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Non-coding RNA Research Pub Date : 2025-12-01 Epub Date: 2025-08-13 DOI:10.1016/j.ncrna.2025.08.002

Yusi Chen , Tengteng Zhu , Fang Li , Yingjie Tan , Tianyu Wang , Xiaoqin Luo , Jun Luo , Yi Tang , Jianqiang Peng , Jiang Li

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引用次数: 0

Abstract

Introduction

tRNA-derived small RNAs (tsRNAs) are emerging as noninvasive biomarkers of cellular damage. However, their role in pulmonary arterial hypertension (PAH) remains unclear.

Methods

Plasma i-tRF-15:31-Lys-CTT-1 levels were quantified in a discovery cohort (n = 141 PAH patients; n = 50 controls) and a verification cohort (n = 254 PAH patients; n = 70 controls). Diagnostic performance was assessed using receiver operating characteristic analysis, and survival outcomes were evaluated with Kaplan-Meier curves and multivariable Cox regression models.

Results

In discovery cohort, the median age was 41 years (IQR 27–54), with 65.9 % female and a median REVEAL 2.0 score of 7 (IQR 6–8). In verification cohort, the median age was 36 years (IQR 31–52), with 63.4 % female and a median REVEAL 2.0 score of 6 (IQR 4–7). i-tRF-15:31-Lys-CTT-1 showed the greatest fold change among tsRNAs in idiopathic PAH (P < 0.0001). Levels of i-tRF-15:31-Lys-CTT-1 were significantly lower in the high-risk REVEAL group (P < 0.0001). The area under the curve (AUC) of i-tRF-15:31-Lys-CTT-1 for idiopathic PAH diagnosis was 0.90 in discovery cohort and 0.81 in verification cohort. Kaplan-Meier analysis revealed that lower i-tRF-15:31-Lys-CTT-1 levels correlated with poorer prognosis (P < 0.0001). After adjusting for age, sex, and BMI, patients in the highest quartile had a significantly lower incidence of clinical events compared to those in the lowest quartile (HR = 0.08; 95 % CI 0.032–0.18; P < 0.001). Incorporating i-tRF-15:31-Lys-CTT-1 into the REVEAL 2.0 model improved predictive accuracy (AUC from 0.67 to 0.75, P < 0.0001).

Conclusions

i-tRF-15:31-Lys-CTT-1 levels are decreased in PAH, correlate with disease severity, and are promising to improve clinical diagnosis and risk stratification.

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血浆trna来源的小RNA i-tRF-15:31-Lys-CTT-1作为肺动脉高压诊断和预后的生物标志物的鉴定

trna衍生的小rna （tsrna）正在成为细胞损伤的非侵入性生物标志物。然而，它们在肺动脉高压（PAH）中的作用尚不清楚。方法在发现队列（n = 141例PAH患者，n = 50对照）和验证队列（n = 254例PAH患者，n = 70对照）中定量测定血浆i-tRF-15:31-Lys-CTT-1水平。采用受试者工作特征分析评估诊断效果，采用Kaplan-Meier曲线和多变量Cox回归模型评估生存结果。结果在发现队列中，年龄中位数为41岁（IQR 27-54），女性占65.9%,REVEAL 2.0分中位数为7分（IQR 6-8）。在验证队列中，中位年龄为36岁（IQR 31-52），其中63.4%为女性，中位REVEAL 2.0评分为6 （IQR 4-7）。i-tRF-15:31-Lys-CTT-1在特发性PAH的tsRNAs中表现出最大的折叠变化（P < 0.0001）。高危REVEAL组i-tRF-15:31-Lys-CTT-1水平显著降低（P < 0.0001）。i-tRF-15:31-Lys-CTT-1诊断特发性多环芳烃的曲线下面积（AUC）在发现组为0.90，在验证组为0.81。Kaplan-Meier分析显示较低的i-tRF-15:31-Lys-CTT-1水平与较差的预后相关（P < 0.0001）。在调整了年龄、性别和BMI后，最高四分位数的患者的临床事件发生率明显低于最低四分位数的患者（HR = 0.08; 95% CI 0.032-0.18; P < 0.001）。将i-tRF-15:31-Lys-CTT-1纳入REVEAL 2.0模型提高了预测精度（AUC从0.67到0.75,P < 0.0001）。结论- trf -15:31- lys - ctt -1水平在PAH中降低，与疾病严重程度相关，有望改善临床诊断和风险分层。

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来源期刊

Non-coding RNA Research Medicine-Biochemistry (medical)

CiteScore

7.70

自引率

6.00%

发文量

审稿时长

49 days

期刊介绍： Non-coding RNA Research aims to publish high quality research and review articles on the mechanistic role of non-coding RNAs in all human diseases. This interdisciplinary journal will welcome research dealing with all aspects of non-coding RNAs-their biogenesis, regulation and role in disease progression. The focus of this journal will be to publish translational studies as well as well-designed basic studies with translational and clinical implications. The non-coding RNAs of particular interest will be microRNAs (miRNAs), small interfering RNAs (siRNAs), small nucleolar RNAs (snoRNAs), U-RNAs/small nuclear RNAs (snRNAs), exosomal/extracellular RNAs (exRNAs), Piwi-interacting RNAs (piRNAs) and long non-coding RNAs. Topics of interest will include, but not limited to: -Regulation of non-coding RNAs -Targets and regulatory functions of non-coding RNAs -Epigenetics and non-coding RNAs -Biological functions of non-coding RNAs -Non-coding RNAs as biomarkers -Non-coding RNA-based therapeutics -Prognostic value of non-coding RNAs -Pharmacological studies involving non-coding RNAs -Population based and epidemiological studies -Gene expression / proteomics / computational / pathway analysis-based studies on non-coding RNAs with functional validation -Novel strategies to manipulate non-coding RNAs expression and function -Clinical studies on evaluation of non-coding RNAs The journal will strive to disseminate cutting edge research, showcasing the ever-evolving importance of non-coding RNAs in modern day research and medicine.