Abstract
BackgroundIn the present study the blood expression level of inflammatory response and autoimmunity associated long non-coding RNAs (lncRNAs) were compared in patients with different chronic respiratory diseases and investigated whether they could be used as biomarkers in these diseases.MethodsIn the discovery cohort, the gene expression level of 84 lncRNAs were measured in the blood of 24 adult patients including healthy controls and patients with asthma and COPD. In the replication cohort the expression of 6 selected lncRNAs were measured in 163 subjects including healthy controls and adults with allergic rhinitis, asthma, COPD and children with asthma. It was evaluated whether these lncRNAs can be used as diagnostic biomarkers for any studied disease. With systems biology analysis the biological functions of the selected lncRNAs were predicted.ResultsIn the discovery cohort, the mean expression of 27 lncRNAs showed nominally significant differences in at least one comparison. OIP5-AS1, HNRNPU, RP11-325K4.3, JPX, RP11-282O18.3, MZF1-AS1 were selected for measurement in the replication cohort. Three lncRNAs (HNRNPU, RP11-325K4.3, JPX) expressed significantly higher in healthy children than in adult controls. All the mean expression level of the 6 lncRNAs differed significantly between adult allergic rhinitis patients and controls. RP11-325K4.3, HNRNPU and OIP5-AS1 expressed higher in allergic asthma than in non-allergic asthma. COPD and asthma differed in the expression of RP11-325K4.3 from each other. In examining of the lncRNAs as biomarkers the weighted accuracy (WA) values were especially high in the comparison of healthy controls and patients with allergic rhinitis. OIP5-AS1 and JPX achieved 0.98 and 0.9 WA values, respectively, and the combination of the selected lncRNAs also resulted in a high performance (WA = 0.98). Altogether, OIP5-AS1 had the highest discriminative power in case of three out of six comparisons.ConclusionDifferences were detected in the expression of circulating lncRNAs in chronic respiratory diseases. Some of these differences might be utilized as biomarkers and also suggest a possible role of these lncRNAs in the pathomechanism of these diseases. The lncRNAs and the associated pathways are potential therapeutic targets in these diseases, but naturally additional studies are needed for the confirmation of these results.
Highlights
In the present study the blood expression level of inflammatory response and autoimmunity associated long non-coding Ribonucleic acid (RNA) were compared in patients with different chronic respiratory diseases and investigated whether they could be used as biomarkers in these diseases
Results of the discovery study In the discovery group, using a prefabricated human inflammatory response and autoimmunity array, the expression levels of 84 Long non-coding RNA (lncRNA) were measured in the blood of 6 patients with mild or moderate asthma (GINA 1–3), 6 with severe asthma (GINA 4–5), 6 with chronic obstructive pulmonary disease (COPD), and in 6 healthy controls (Table 1)
Among the lncRNAs on the panel, there were 2 lncRNAs which showed inherently different expressions in the two genders: X-inactive specific transcript (XIST), which is involved in the inactivation of the X chromosome in women, and NAV2-AS5, which is mainly expressed in the testis
Summary
In the present study the blood expression level of inflammatory response and autoimmunity associated long non-coding RNAs (lncRNAs) were compared in patients with different chronic respiratory diseases and investigated whether they could be used as biomarkers in these diseases. Chronic respiratory diseases such as asthma, chronic obstructive pulmonary disease (COPD) and allergic rhinitis cause an enormous burden on the societies and are considered as major non-communicable diseases [1]. Over 1 billion people in the world suffer from chronic respiratory diseases [2, 3]. COPD has an estimated annual death rate of over 4 million people globally [8, 9]
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