García-Sánchez Asunción, Estravís Miguel, Martin Maria J, Pérez-Pazos Jacqueline, Martín-García Cristina, Gil-Melcón María, Ramos-González Jacinto, Eguiluz-Gracia Ibon, Triviño Juan Carlos, Isidoro-García María, Dávila Ignacio, Sanz Catalina
Grupo Alergología, Instituto de Investigación Biomédica de Salamanca (IBSAL), 37007 Salamanca, Spain.
Red Cooperativa de Investigación en Salud-RETICS ARADyAL, 37007 Salamanca, Spain.
J Pers Med. 2021 Aug 24;11(9):827. doi: 10.3390/jpm11090827.
Precision medicine is a promising strategy to identify biomarkers, stratify asthmatic patients according to different endotypes, and match them with the appropriate therapy. This proof-of-concept study aimed to investigate whether gene expression in peripheral blood could provide a valuable noninvasive approach for the molecular phenotyping of asthma.
We performed whole-transcriptome RNA sequencing on peripheral blood of 30 non-atopic non-asthmatic controls and 30 asthmatic patients. A quantitative PCR (qPCR) validation study of that encodes for CRTH2 receptor, expressed in cells involved in T2 inflammation, was developed in a cohort of 361 independent subjects: 94 non-asthmatic non-atopic controls, 187 asthmatic patients [including 82 with chronic rhinosinusitis with nasal polyposis (CRSwNP) and 24 with aspirin-exacerbated respiratory disease (AERD)], 52 with allergic rhinitis, and 28 with CRSwNP without asthma.
was one of the most differentially overexpressed genes in asthmatic patients' peripheral blood (-value 2.64 × 10). These results were confirmed by qPCR in the validation study, where transcripts were significantly upregulated in asthmatic patients ( < 0.001). This upregulation was mainly detected in some subgroups such as allergic asthma, asthma with CRSwNP, AERD, eosinophilic asthma, and severe persistent asthma. expression was detected in different blood cell types, and its correlation with eosinophil counts showed differences in some groups of asthmatic patients.
We found that expression levels could identify asthma patients, introduce a minimally invasive biomarker for adult asthma molecular phenotyping, and add additional information to blood eosinophils. Although further studies are required, analyzing expression levels in peripheral blood of asthmatics might assist in selecting patients for treatment with specific antagonists.
精准医学是一种很有前景的策略，可用于识别生物标志物、根据不同的内型对哮喘患者进行分层，并为他们匹配合适的治疗方法。这项概念验证研究旨在调查外周血中的基因表达是否能为哮喘的分子表型分析提供一种有价值的非侵入性方法。
我们对30名非特应性非哮喘对照者和30名哮喘患者的外周血进行了全转录组RNA测序。在一个由361名独立受试者组成的队列中开展了一项针对编码CRTH2受体的基因的定量PCR（qPCR）验证研究，该受体在参与2型炎症的细胞中表达：94名非哮喘非特应性对照者、187名哮喘患者[包括82名伴有鼻息肉的慢性鼻-鼻窦炎（CRSwNP）患者和24名阿司匹林诱发的呼吸道疾病（AERD）患者]、52名变应性鼻炎患者以及28名无哮喘的CRSwNP患者。
该基因是哮喘患者外周血中差异表达最为明显的过表达基因之一（-值为2.64×10）。这些结果在验证研究中通过qPCR得到了证实，在该研究中，哮喘患者的该基因转录本显著上调（<0.001）。这种上调主要在一些亚组中检测到，如过敏性哮喘、伴有CRSwNP的哮喘、AERD、嗜酸性粒细胞性哮喘和重度持续性哮喘。该基因在不同血细胞类型中均有表达，并且其与嗜酸性粒细胞计数的相关性在某些哮喘患者组中存在差异。
我们发现该基因的表达水平可识别哮喘患者，为成人哮喘分子表型分析引入一种微创生物标志物，并为血液嗜酸性粒细胞补充额外信息。尽管还需要进一步研究，但分析哮喘患者外周血中的该基因表达水平可能有助于选择接受特定拮抗剂治疗的患者。
