一种用于扩张型心肌病分子诊断的新型六长非编码RNA特征的鉴定
Identification of a Novel Six-Long Noncoding RNA Signature for Molecular Diagnosis of Dilated Cardiomyopathy.
作者信息
Zhang Hui, Chen Xiajing, Zhang Danfeng, Liu Lingjuan, Song Jing, Xu Yinyin, Tian Jie
机构信息
Department of Cardiology, Heart Centre, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, Chongqing Key Laboratory of Pediatrics, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, People's Republic of China.
Department of Bioinformatics, The Basic Medical School, Chongqing Medical University, Chongqing, China.
出版信息
DNA Cell Biol. 2020 Nov 3. doi: 10.1089/dna.2020.5670.
Long noncoding RNAs (lncRNAs) may serve as potential molecular diagnostic markers to improve the capacity of earlier and more accurate diagnosis of dilated cardiomyopathy (DCM). We integrated five independent transcriptomic datasets ( = 504) from Gene Expression Omnibus for systematic identification of lncRNA-based diagnostic biomarkers in DCM. The multivariate logistic regression model based on the six lncRNAs (, , , , , and ) in the ceRNA networks showed high sensitivity and specificity (area under curves >0.8, < 0.0001) of DCM diagnosis in the training and validation datasets. Functional analysis revealed that the autophagy, protein acetyltransferase, and DNA polymerase activity were associated with high levels of the six-lncRNA signature, while the collagen trimer, extracellular matrix structural constituent, and MHC protein complex were associated with low levels of the signature. Pathway analysis showed that high levels of the six-lncRNA signature were associated with upregulated selective autophagy, interleukin 17 signalings, and extracellular matrix interactions, while were associated with downregulated extracellular matrix organization and collagen formation. The identified six-lncRNA signature, with high performance in molecular diagnosis of DCM, might be applied in future clinical practices combined with traditional markers.
长链非编码RNA(lncRNAs)可能作为潜在的分子诊断标志物,以提高扩张型心肌病(DCM)早期诊断和更准确诊断的能力。我们整合了来自基因表达综合数据库的五个独立转录组数据集(n = 504),用于系统鉴定DCM中基于lncRNA的诊断生物标志物。基于ceRNA网络中六种lncRNA(......,此处原文六种lncRNA名称缺失)的多变量逻辑回归模型在训练和验证数据集中显示出DCM诊断的高敏感性和特异性(曲线下面积>0.8,P < 0.0001)。功能分析表明,自噬、蛋白质乙酰转移酶和DNA聚合酶活性与六种lncRNA特征的高水平相关,而胶原三聚体、细胞外基质结构成分和MHC蛋白复合物与该特征的低水平相关。通路分析表明,六种lncRNA特征的高水平与选择性自噬、白细胞介素17信号通路和细胞外基质相互作用的上调相关,而与细胞外基质组织和胶原形成的下调相关。所鉴定的六种lncRNA特征在DCM的分子诊断中具有高性能,可能在未来临床实践中与传统标志物联合应用。