Plasma Extracellular Vesicle miRNAs Can Identify Lung Cancer, Current Smoking Status, and Stable COPD

Abstract

Lung cancer remains the leading cause of cancer related mortality worldwide. We aimed to test whether a simple blood biomarker (extracellular vesicle miRNAs) can discriminate between cases with and without lung cancer. Methods: plasma extracellular vesicles (EVs) were isolated from four cohorts (n = 20 in each): healthy non-smokers, healthy smokers, lung cancer, and stable COPD participants. EV miRNA expression was evaluated using the miRCURY LNA miRNA Serum/Plasma assay for 179 specific targets. Significantly dysregulated miRNAs were assessed for discriminatory power using ROC curve analysis. Results: 15 miRNAs were differentially expressed between lung cancer and healthy non-smoking participants, with the greatest single miRNA being miR-205-5p (AUC 0.850), improving to AUC 0.993 in combination with miR-199a-5p. Moreover, 26 miRNAs were significantly dysregulated between lung cancer and healthy smoking participants, with the greatest single miRNA being miR-497-5p (AUC 0.873), improving to AUC 0.953 in combination with miR-22-5p; 14 miRNAs were significantly dysregulated between lung cancer and stable COPD participants, with the greatest single miRNA being miR-27a-3p (AUC 0.803), with two other miRNAs (miR-106b-3p and miR-361-5p) further improving discriminatory power (AUC 0.870). Conclusion: this case control study suggests miRNAs in EVs from plasma holds key biological information specific for lung cancer and warrants further prospective assessment.

miR-199a: A Tumor Suppressor with Noncoding RNA Network and Therapeutic Candidate in Lung Cancer

“…are significantly enriched in EVs in blood during lung infection and injury [ 125 ], and these miRNAs play important regulatory roles. Coincidentally, O’Farrell, H.E et al demonstrated [ 126 ] that miRNAs in EVs from plasma have key biological information specific to lung cancer. Fifteen miRNAs, including miR-199a-5p, were differentially expressed between lung cancer patients and healthy non-smoking participants.…”

EVs-miRNA: The New Molecular Markers for Chronic Respiratory Diseases

“…A further study made it possible to identify EVs-miRNAs as diagnostic biomarkers to distinguish patients with lung cancer and patients with COPD, as well as to determine the differences between smokers suffering from these pathologies [ 83 ]. In this study, O’Farrell et al have demonstrated the applicability of EVs-miRNAs as a screening tool for patients with COPD or lung cancer.…”

Role of microRNAs in type 2 diseases and allergen-specific immunotherapy

“…Furthermore, it has also been reported that airway inflammation and airway remodeling are exacerbated by activation of JNK1/2-MMP-9 pathway associated with ORMDL3 knockdown in asthmatic mice, suggesting that miR-192-5p mediates airway remodeling and autophagy by other signaling pathways (65). Abnormal expression has been reported for miR-451a in pulmonary diseases associated with remodeling processes, as elevated levels of expression have been demonstrated in patients with chronic obstructive pulmonary disease (COPD) (66). Several miRs, such as miR-19a, miR-142, and miR-221, have been found to be differentially expressed in asthma and associated with airway remodeling (67)(68)(69).…”