<i>PTGDR2</i> Expression in Peripheral Blood as a Potential Biomarker in Adult Patients with Asthma

• Main Authors: Asunción García-Sánchez, Miguel Estravís, Maria J. Martin, Jacqueline Pérez-Pazos, Cristina Martín-García, María Gil-Melcón, Jacinto Ramos-González, Ibon Eguiluz-Gracia, Juan Carlos Triviño, María Isidoro-García, Ignacio Dávila, Catalina Sanz
• Format: Article
• Language: English
• Published: MDPI AG 2021-08-01
• Series: Journal of Personalized Medicine
• Subjects: aspirin exacerbated respiratory disease (AERD); asthma; biomarker; chronic rhinosinusitis with nasal polyps (CRSwNP); gene expression; <i>PTGDR2</i>
• Online Access: https://www.mdpi.com/2075-4426/11/9/827

Background: 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. Methods: 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 <i>PTGDR2</i> 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. Results: <i>PTGDR2</i> was one of the most differentially overexpressed genes in asthmatic patients’ peripheral blood (<i>p</i>-value 2.64 × 10⁶). These results were confirmed by qPCR in the validation study, where <i>PTGDR2</i> transcripts were significantly upregulated in asthmatic patients (<i>p</i> < 0.001). This upregulation was mainly detected in some subgroups such as allergic asthma, asthma with CRSwNP, AERD, eosinophilic asthma, and severe persistent asthma. <i>PTGDR2</i> expression was detected in different blood cell types, and its correlation with eosinophil counts showed differences in some groups of asthmatic patients. Conclusions: We found that <i>PTGDR2</i> 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 <i>PTGDR2</i> expression levels in peripheral blood of asthmatics might assist in selecting patients for treatment with specific antagonists.