呼吸道合胞病毒细支气管炎婴儿疾病严重程度的鼻腔微小RNA特征：一项多中心前瞻性研究
Nasal microRNA signatures for disease severity in infants with respiratory syncytial virus bronchiolitis: a multicentre prospective study.
作者信息
Kyo Michihito, Zhu Zhaozhong, Shibata Ryohei, Ooka Tadao, Mansbach Jonathan M, Harmon Brennan, Hahn Andrea, Pérez-Losada Marcos, Camargo Carlos A, Hasegawa Kohei
机构信息
Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
出版信息
BMJ Open Respir Res. 2024 Jul 31;11(1):e002288. doi: 10.1136/bmjresp-2023-002288.
BACKGROUND
Respiratory syncytial virus (RSV) bronchiolitis contributes to a large morbidity and mortality burden globally. While emerging evidence suggests that airway microRNA (miRNA) is involved in the pathobiology of RSV infection, its role in the disease severity remains unclear.
METHODS
In this multicentre prospective study of infants (aged<1 year) hospitalised for RSV bronchiolitis, we sequenced the upper airway miRNA and messenger RNA (mRNA) at hospitalisation. First, we identified differentially expressed miRNAs (DEmiRNAs) associated with higher bronchiolitis severity-defined by respiratory support (eg, positive pressure ventilation, high-flow oxygen therapy) use. We also examined the biological significance of miRNAs through pathway analysis. Second, we identified differentially expressed mRNAs (DEmRNAs) associated with bronchiolitis severity. Last, we constructed miRNA-mRNA coexpression networks and determined hub mRNAs by weighted gene coexpression network analysis (WGCNA).
RESULTS
In 493 infants hospitalised with RSV bronchiolitis, 19 DEmiRNAs were associated with bronchiolitis severity (eg, miR-27a-3p, miR-26b-5p; false discovery rate<0.10). The pathway analysis using miRNA data identified 1291 bronchiolitis severity-related pathways-for example, regulation of cell adhesion mediated by integrin. Second, 1298 DEmRNAs were associated with bronchiolitis severity. Last, of these, 190 DEmRNAs were identified as targets of DEmiRNAs and negatively correlated with DEmiRNAs. By applying WGCNA to DEmRNAs, four disease modules were significantly associated with bronchiolitis severity-for example, microtubule anchoring, cell-substrate junction. The hub genes for each of these modules were also identified-for example, for the microtubule anchoring module, for the cell-substrate junction module.
CONCLUSIONS
In infants hospitalised for RSV bronchiolitis, airway miRNA-mRNA coexpression network contributes to the pathobiology of bronchiolitis severity.
背景
呼吸道合胞病毒（RSV）细支气管炎在全球范围内造成了巨大的发病和死亡负担。虽然新出现的证据表明气道微小RNA（miRNA）参与了RSV感染的病理生物学过程，但其在疾病严重程度中的作用仍不清楚。
方法
在这项针对因RSV细支气管炎住院的婴儿（年龄<1岁）的多中心前瞻性研究中，我们在住院时对上呼吸道miRNA和信使核糖核酸（mRNA）进行了测序。首先，我们确定了与较高细支气管炎严重程度相关的差异表达miRNA（DEmiRNA），细支气管炎严重程度由呼吸支持（如正压通气、高流量氧疗）的使用来定义。我们还通过通路分析研究了miRNA的生物学意义。其次，我们确定了与细支气管炎严重程度相关的差异表达mRNA（DEmRNA）。最后，我们构建了miRNA-mRNA共表达网络，并通过加权基因共表达网络分析（WGCNA）确定了枢纽mRNA。
结果
在493例因RSV细支气管炎住院的婴儿中，19种DEmiRNA与细支气管炎严重程度相关（如miR-27a-3p、miR-26b-5p；错误发现率<0.10）。使用miRNA数据进行的通路分析确定了1291条与细支气管炎严重程度相关的通路，例如整合素介导的细胞黏附调节。其次，1298种DEmRNA与细支气管炎严重程度相关。最后，在这些DEmRNA中，190种被确定为DEmiRNA的靶标，且与DEmiRNA呈负相关。通过将WGCNA应用于DEmRNA，四个疾病模块与细支气管炎严重程度显著相关，例如微管锚定、细胞-基质连接。还确定了每个模块的枢纽基因，例如，微管锚定模块的枢纽基因，细胞-基质连接模块的枢纽基因。
结论
在因RSV细支气管炎住院的婴儿中，气道miRNA-mRNA共表达网络有助于细支气管炎严重程度的病理生物学过程。
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