| Summary: | Despite rapidly evolving pathobiological mechanistic demystification, coupled with advances in diagnostic and therapeutic modalities, chronic obstructive pulmonary disease (COPD) remains a major healthcare and clinical challenge, globally. Further compounded by the dearth of available curative anti-COPD therapy, it is posited that this challenge may not be dissociated from the current lack of actionable COPD pathognomonic molecular biomarkers. There is accruing evidence of the involvement of protracted ‘smoldering’ inflammation, repeated lung injury, and accelerated lung aging in enhanced predisposition to or progression of COPD. The relatively novel uncharacterized human long noncoding RNA <i>lnc-IL7R</i> (otherwise called LOC100506406) is increasingly designated a negative modulator of inflammation and regulator of cellular stress responses; however, its role in pulmonary physiology and COPD pathogenesis remains largely unclear and underexplored. Our previous work suggested that upregulated <i>lnc-IL7R</i> expression attenuates inflammation following the activation of the toll-like receptor (TLR)-dependent innate immune system, and that the upregulated <i>lnc-IL7R</i> is anti-correlated with concomitant high PM<sub>2.5</sub>, PM<sub>10</sub>, and SO<sub>2</sub> levels, which is pathognomonic for exacerbated/aggravated COPD in Taiwan. In the present study, our quantitative analysis of <i>lnc-IL7R</i> expression in our COPD cohort (n = 125) showed that the <i>lnc-IL7R</i> level was significantly correlated with physiological pulmonary function and exhibited COPD-based stratification implications (area under the curve, AUC = 0.86, <i>p</i> < 0.001). We found that the <i>lnc-IL7R</i> level correctly identified patients with COPD (sensitivity = 0.83, specificity = 0.83), precisely discriminated those without emphysematous phenotype (sensitivity = 0.48, specificity = 0.89), and its differential expression reflected disease course based on its correlation with the COPD GOLD stage (r = −0.59, <i>p</i> < 0.001), %LAA<sub>-950insp</sub> (r = −0.30, <i>p</i> = 0.002), total LAA (r = −0.35, <i>p</i> < 0.001), FEV<sub>1</sub>(%) (r = 0.52, <i>p</i> < 0.001), FVC (%) (r = 0.45, <i>p</i> < 0.001), and post-bronchodilator FEV<sub>1</sub>/FVC (r = 0.41, <i>p</i> < 0.001). Consistent with other data, our bioinformatics-aided dose–response plot showed that the probability of COPD decreased as <i>lnc-IL7R</i> expression increased, thus, corroborating our posited anti-COPD therapeutic potential of <i>lnc-IL7R</i>. In conclusion, reduced <i>lnc-IL7R</i> expression not only is associated with inflammation in the airway epithelial cells but is indicative of impaired pulmonary function, pathognomonic of COPD, and predictive of an exacerbated/ aggravated COPD phenotype. These data provide new mechanistic insights into the ailing lung and COPD progression, as well as suggest a novel actionable molecular factor that may be exploited as an efficacious therapeutic strategy in patients with COPD.
|
|---|