Cell‐free microRNAs (miRNAs) are transferred in disease state including inflammatory lung diseases and are often packed into extracellular vesicles (EVs). To assess their suitability as biomarkers for community‐acquired pneumonia (CAP) and severe secondary complications such as sepsis, we studied patients with CAP (n = 30), sepsis (n = 65) and healthy volunteers (n = 47) subdivided into a training (n = 67) and a validation (n = 75) cohort. After precipitating crude EVs from sera, associated small RNA was profiled by next‐generation sequencing (NGS) and evaluated in multivariate analyses. A subset of the thereby identified biomarker candidates was validated both technically and additionally by reverse transcription quantitative real‐time PCR (RT‐qPCR). Differential gene expression (DGE) analysis revealed 29 differentially expressed miRNAs in CAP patients when compared to volunteers, and 25 miRNAs in patients with CAP, compared to those with sepsis. Sparse partial‐least discriminant analysis separated groups based on 12 miRNAs. Three miRNAs proved as a significant biomarker signature. While expression levels of miR‐1246 showed significant changes with an increase in overall disease severity from volunteers to CAP and to sepsis, miR‐193a‐5p and miR‐542‐3p differentiated patients with an infectious disease (CAP or sepsis) from volunteers. Cell‐free miRNAs are potentially novel biomarkers for CAP and may help to identify patients at risk for progress to sepsis, facilitating early intervention and treatment.

中文翻译：

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循环性无细胞microRNA对社区获得性肺炎和与肺炎相关的败血症的诊断潜力。

无细胞的microRNA（miRNA）以包括炎症性肺部疾病在内的疾病状态转移，通常被包装到细胞外囊泡（EVs）中。为了评估其作为社区获得性肺炎（CAP）和严重继发性并发症（如败血症）的生物标志物的适用性，我们研究了CAP（n = 30），败血症（n = 65）和健康志愿者（n = 47）细分为训练（n = 67）和验证（n = 75）队列。从血清中沉淀出粗制电动汽车后，通过下一代测序（NGS）对相关的小RNA进行分析，并在多变量分析中进行评估。由此鉴定的生物标志物候选物的一部分在技术上以及通过逆转录定量实时PCR（RT-qPCR）进行了验证。差异基因表达（DGE）分析显示，与志愿者相比，CAP患者中29种差异表达的miRNA，与败血症患者相比，CAP患者中具有25种miRNA。稀疏的偏最少判别分析基于12个miRNA分离了各组。三种miRNA被证明是重要的生物标志物签名。从志愿者到CAP和败血症，miR-1246的表达水平随总体疾病严重程度的增加而发生显着变化，而miR-193a-5p和miR-542-3p的感染性疾病（CAP或败血症）则与志愿者有所区别。无细胞的miRNAs可能是CAP的新型生物标志物，可能有助于鉴定有进展为败血症风险的患者，从而促进早期干预和治疗。与败血症相比。稀疏的偏最少判别分析基于12个miRNA分离了各组。三种miRNA被证明是重要的生物标志物签名。尽管从志愿者到CAP和败血症，miR-1246的表达水平随总体疾病严重程度的增加而发生了显着变化，但miR-193a-5p和miR-542-3p的感染性患者（CAP或败血症）与志愿者有所区别。无细胞的miRNA可能是CAP的新型生物标志物，可能有助于鉴定有进展为败血症风险的患者，从而有助于早期干预和治疗。与败血症相比。稀疏的偏最少判别分析基于12个miRNA分离了各组。三种miRNA被证明是重要的生物标志物签名。从志愿者到CAP和败血症，miR-1246的表达水平随总体疾病严重程度的增加而发生显着变化，而miR-193a-5p和miR-542-3p的感染性疾病（CAP或败血症）则与志愿者有所区别。无细胞的miRNAs可能是CAP的新型生物标志物，可能有助于鉴定有进展为败血症风险的患者，从而促进早期干预和治疗。从志愿者到CAP和败血症，miR-1246的表达水平随总体疾病严重程度的增加而发生显着变化，而miR-193a-5p和miR-542-3p的感染性疾病（CAP或败血症）则与志愿者有所区别。无细胞的miRNA可能是CAP的新型生物标志物，可能有助于鉴定有进展为败血症风险的患者，从而有助于早期干预和治疗。从志愿者到CAP和败血症，miR-1246的表达水平随总体疾病严重程度的增加而发生显着变化，而miR-193a-5p和miR-542-3p的感染性疾病（CAP或败血症）则与志愿者有所区别。无细胞的miRNAs可能是CAP的新型生物标志物，可能有助于鉴定有进展为败血症风险的患者，从而促进早期干预和治疗。