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 (n = 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 (AC016722.3, AL589986.2, AC006007.1, AC092687.3, GS1-124K5.4, and AC007126.1) in the ceRNA networks showed high sensitivity and specificity (area under curves >0.8, p < 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.

中文翻译：

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新型六长非编码RNA签名的扩张型心肌病的分子诊断。

长的非编码RNA（lncRNA）可以用作潜在的分子诊断标记，以提高早期和更准确的扩张型心肌病（DCM）诊断能力。我们整合了 来自Gene Expression Omnibus的五个独立的转录组数据集（n = 504），用于系统鉴定DCM中基于lncRNA的诊断生物标记物。ceRNA网络中基于六个lncRNAs（AC016722.3，AL589986.2，AC006007.1，AC092687.3，GS1-124K5.4和AC007126.1）的多元logistic回归模型显示出高灵敏度和特异性（曲线> 0.8，p 训练和验证数据集中DCM诊断的<0.0001）。功能分析表明，自噬，蛋白乙酰转移酶和DNA聚合酶活性与高水平的6-lncRNA签名相关，而胶原三聚体，细胞外基质结构成分和MHC蛋白复合物与低水平的签名相关。通路分析表明，高水平的六-lncRNA签名与选择性自噬，白介素17信号传导和细胞外基质相互作用上调相关，而与细胞外基质组织和胶原蛋白形成下调相关。所鉴定的六-lncRNA标记物在DCM的分子诊断中具有较高的性能，可与传统标记物结合用于未来的临床实践中。