<p>Confounding Patient Factors Affecting the Proper Interpretation of the Periostin Level as a Biomarker in Asthma Development</p>

Abstract

Introduction: The proper use of serum periostin (POSTN) as a biomarker for asthma is hindered by inconsistent performance in different clinical settings. Objective: To explore patient's factors that may affect POSTN expression locally and systematically and its utility as a biomarker for asthma development. Materials and Methods: Here we used bioinformatics analysis of publicly available transcriptomics data to confirm that POSTN is an asthma specific gene involved in core signaling pathways enriched in the bronchial epithelium during asthma. We then explored a large number of datasets to identify possible confounders that may affect the POSTN gene expression and consequently, its interpretation as a reliable biomarker for asthma. Plasma and saliva levels of POSTN were determined in locally recruited asthmatic patients (mild, moderate and severe) compared to healthy controls to confirm the bioinformatics findings. Results: Our bioinformatics results confirmed that POSTN was consistently upregulated in the bronchial epithelium in asthma, chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) bronchial epithelium. In asthma, its mRNA expression was affected by gender, sample anatomical site and type, steroid therapy, and smoking. In our cohort, plasma POSTN was upregulated in severe and non-severe asthmatic patients. Saliva POSTN was significantly higher in non-severe asthmatic patients compared to healthy and severe asthmatic patients (specifically those who are not on Xolair (omalizumab)). Patients' BMI, inhaled steroid use and Xolair treatment affected POSTN plasma levels. Conclusion: Up to our knowledge, this is the first study examining the level of POSTN in the saliva of asthmatic patients. Both plasma and saliva POSTN levels can aid in early diagnosis of asthma. Saliva POSTN level was more sensitive than plasma POSTN in differentiating between severe and non-severe asthmatics. Patients' characteristics like BMI, the use of inhaled steroids, or Xolair treatment should be carefully reviewed before any meaningful interpretation of POSTN level in clinical practice.

Pathological Roles and Clinical Usefulness of Periostin in Type 2 Inflammation and Pulmonary Fibrosis

“…For example, baseline periostin levels are high in paediatric serum [177], which may mask changes due to local release in the lesion site and reduce the usefulness of periostin biomarker. The gender difference for periostin expression was higher in males than in females in the bronchial epithelium of healthy controls [156]. Additionally, in the bronchial epithelium of asthma, only females expressed higher levels of POSTN mRNA (males did not) compared to healthy controls.…”

“…Since periostin is easily secreted into biological fluids, periostin is detected in not only serum but also local biological samples such as tear [78], vitreous fluid [141][142][143], nasal lavage fluid [144], bronchoalveolar lavage fluid [145][146][147], sputum [148][149][150][151][152][153], exhaled breath condensate [154,155], saliva [156][157][158], gingival crevicular fluid [159] and urine [160][161][162][163] (Table 2). Therefore, periostin in several biological fluids may be used as a sensitive diagnostic or prognostic biomarker under various pathological conditions.…”

“…Interestingly, the use of some biologics and high doses of ICS has also been reported to decrease periostin levels [122,[170][171][172][173]. Patients with severe asthma who were not specifically using Xolair had higher plasma periostin concentrations than healthy controls [156], and using Xolair was shown to reduce periostin levels in patients with severe asthma [170,173]. Thus, the use of Xolair treatment may affect the serum/plasma levels of periostin, suggesting periostin may be a possible monitoring marker.…”

Inhibition of Postn Rescues Myogenesis Defects in Myotonic Dystrophy Type 1 Myoblast Model

“…These results imply a potential regulatory role of Postn in DM1 pathogenesis. Previous studies have indicated that Postn could serve as serum biomarkers for many diseases, including cancer ( Dong et al, 2018a , b ), rhinosinusitis ( Ninomiya et al, 2018 ), and asthma ( Hachim et al, 2020 ). Based on the upregulations of Postn in the DM1 myoblast cell model and the skeletal muscle and myoblasts from DM1 patients, we thought Postn might be used as a biomarker for DM1, which, however, needed further verifications of the expressions of Postn in the serum of DM1 patients.…”

Wnt Signaling Is Deranged in Asthmatic Bronchial Epithelium and Fibroblasts

“…To decrease the effect of technical confounding factors on the gene expression, in-house preprocessing QC, normalization, and filtering of raw CEL files extracted from well-characterized publicly available bronchial epithelium transcriptomic datasets were performed as previously described ( Hachim et al, 2019 , 2020a , b ). In brief, the publicly available transcriptomic dataset from GEO was filtered to search for a dataset that includes asthmatic patients with defined clinical classifications of participants compared to healthy controls with different airways sampling from the same subject (central versus peripheral).…”