Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. X:X | DOI: 10.5507/bp.2026.011
Identification of abnormal expression profile of peripheral blood miRNA and its diagnostic value in grading the severity of COPD
- Department of Respiratory Medicine, Affiliated Nanjing Tongren Hospital of Southeast University Medical College, Nanjing 211000, Jiangsu Province, China
Background: Chronic obstructive pulmonary disease (COPD) is now a major contributor to illness and death on a global scale. Traditional classifications based on pulmonary-function variables like the FEV1 (% predicted), lack sensitivity to early inflammatory changes and disease heterogeneity. In contrast, MiRNAs have emerged as promising biomarkers for respiratory conditions including COPD. The aim of this study was to examine the association between selected MiRNAs and COPD.
Methods: A total of 200 COPD patients (GOLD I-IV, n=50 each) and 50 healthy controls were enrolled. Differentially expressed miRNAs were identified from the GEO database and validated by RT-qPCR. Univariate analysis and LASSO regression were used for feature selection. A logistic regression model incorporating selected variables was established for the forecast COPD severity. KEGG pathway enrichment of miR-518b target genes was performed using DAVID.
Results: Five miRNAs (miR-216a, miR-518b, miR-106a, miR-1233, and miR-184) were substantially increased in COPD and correlated with disease severity (P<0.001). LASSO regression identified FEV1 (% predicted), DLCO (% predicted), CAT score, miR-518b, and age as key predictors. The combined model showed excellent classification performance (AUC=0.953; sensitivity=92.9%; specificity=81.3%). MiR-518b emerged as a strong independent risk factor (OR=18.91, P=0.003). Gene set enrichment of miR-518b targets pointed to involvement in both the Toll-like receptor and Hippo pathways, implicating its critical roles in inflammation and airway remodeling.
Conclusions: MiR-518b is closely associated with COPD severity and may be useful in clinical practice. A model integrating miRNA expression and clinical parameters provides high predictive value for COPD classification and supports precision diagnosis.
Keywords: COPD, miR-518b, classification performance
Received: October 14, 2025; Revised: April 10, 2026; Accepted: April 14, 2026; Prepublished online: May 4, 2026
References
- Agustí A, Celli BR, Criner GJ, Halpin D, Anzueto A, Barnes P, Bourbeau J, Han MK, Martinez FJ, de Oca MM, Mortimer K, Papi A, Pavord I, Roche N, Salvi S, Sin DD, Singh D, Stockley R, Varela MVL, Wedzicha JA, Vogelmeier CF. Global Initiative for Chronic Obstructive Lung Disease 2023 Report: GOLD Executive Summary. Respirology 2023;28(4):316-38. doi: 10.1111/resp.14486
Go to original source...
Go to PubMed... - Ding ZQ, Xiao XR, Li N, Sun C, Shi YJ. Association between Streptococcus and chronic obstructive pulmonary disease: A two-sample Mendelian randomization study. Medicine 2025;104(28):e43306. doi: 10.1097/MD.0000000000043306
Go to original source...
Go to PubMed... - Zhu Y, Shen T, Guo RX, Liu K, Cao X, Yang XY, Zhang CT. Global, regional, and national burden of young COPD, 1990-2021, with forecasts to 2050: a systematic analysis for the global burden of disease study 2021. BMC public health 2025;25(1):276. doi: 10.1186/s12889-025-21414-2
Go to original source...
Go to PubMed... - Ulanova MA. Lysozyme activity in the secretions and blood of children with uncomplicated and complicated forms of acute respiratory viral infections. Pediatriia 1983;(2):47-9.
- Li T, Zhou HP, Zhou ZJ, Guo LQ, Zhou LF. Computed tomography-identified phenotypes of small airway obstructions in chronic obstructive pulmonary disease. Chin Med J (Engl) 2021;134(17):2025-36. doi: 10.1097/CM9.0000000000001724
Go to original source...
Go to PubMed... - Yin C, Udrescu M, Gupta G, Cheng M, Lihu A, Udrescu L, Bogdan P, Mannino DM, Mihaicuta S. Fractional Dynamics Foster Deep Learning of COPD Stage Prediction. Adv Sci (Weinh) 2023;10(12):e2203485. doi: 10.1002/advs.202203485
Go to original source...
Go to PubMed... - David B, Bafadhel M, Koenderman L, De Soyza A. Eosinophilic inflammation in COPD: from an inflammatory marker to a treatable trait. Thorax 2021;76(2):188-95. doi: 10.1136/thoraxjnl-2020-215167
Go to original source...
Go to PubMed... - Zeng HZ, Liu XX, Liu PP, Jia SY, Wei GY, Chen G, Zhao L. Exercise's protective role in chronic obstructive pulmonary disease via modulation of M1 macrophage phenotype through the miR-124-3p/ERN1 axis. Sci Prog 2025;108(3):368504251360892. doi: 10.1177/00368504251360892
Go to original source... - Khanna V, Singh K. MicroRNAs as promising drug delivery target to ameliorate chronic obstructive pulmonary disease using nano-carriers: a comprehensive review. Mol Cell Biochem 2025;480(3):1431-48. doi: 10.1007/s11010-024-05110-0
Go to original source...
Go to PubMed... - Lee J, Na HK, Kim WK. Flexible and Reusable Biochip Platform for miRNA Quantification via Dual-Signal Amplification on 3D Au Substrate. Anal Chem 2025;97(28):15208-15. doi: 10.1021/acs.analchem.5c01742
Go to original source...
Go to PubMed... - Yan H, Wen YJ, Tian ZM, Hart N, Han S, Hughes SJ, Zeng Y. A one-pot isothermal Cas12-based assay for the sensitive detection of microRNAs. Nat Biomed Eng 2023;7(12):1583-601. doi: 10.1038/s41551-023-01033-1
Go to original source...
Go to PubMed... - Lv J, Xiong X. Extracellular Vesicle microRNA: A Promising Biomarker and Therapeutic Target for Respiratory Diseases. Int J Mol Sci 2024;25(17):9147. doi: 10.3390/ijms25179147
Go to original source... - Kim RY, Sunkara KP, Bracke KR, Jarnicki AG, Donovan C, Hsu AC, Ieni A, Beckett EL, Galvão I, Wijnant S, Ricciardolo FL, Di Stefano A, Haw TJ, Liu G, Ferguson AL, Palendira U, Wark PA, Conickx G, Mestdagh P, Brusselle GG, Hansbro PM. A microRNA-21-mediated SATB1/S100A9/NF-κB axis promotes chronic obstructive pulmonary disease pathogenesis. Sci Transl Med 2021;13(621):eaav7223. doi: 10.1126/scitranslmed.aav7223
Go to original source... - Nouws J, Wan F, Finnemore E, Roque W, Kim SJ, Bazan I, Li CX, Skold CM, Dai Q, Yan X, Chioccioli M, Neumeister V, Britto CJ, Sweasy J, Bindra R, Wheelock ÅM, Gomez JL, Kaminski N, Lee PJ, Sauler M. MicroRNA miR-24-3p reduces DNA damage responses, apoptosis, and susceptibility to chronic obstructive pulmonary disease. JCI insight 2021;6(2):e134218. doi: 10.1172/jci.insight.134218
Go to original source...
Go to PubMed... - Moisoiu T, Dragomir MP, Iancu SD, Schallenberg S, Birolo G, Ferrero G, Burghelea D, Stefancu A, Cozan RG, Licarete E, Allione A, Matullo G, Iacob G, Bálint Z, Badea RI, Naccarati A, Horst D, Pardini B, Leopold N, Elec F. Combined miRNA and SERS urine liquid biopsy for the point-of-care diagnosis and molecular stratification of bladder cancer. Mol Med 2022;28(1):39. doi: 10.1186/s10020-022-00462-z
Go to original source...
Go to PubMed... - De Smet EG, Mestdagh P, Vandesompele J, Brusselle GG, Bracke KR. Non-coding RNAs in the pathogenesis of COPD. Thorax 2015;70(8):782-91. doi: 10.1136/thoraxjnl-2014-206560
Go to original source...
Go to PubMed... - Osei ET, Florez-Sampedro L, Timens W, Postma DS, Heijink IH, Brandsma CA. Unravelling the complexity of COPD by microRNAs: it's a small world after all. Eur Respir J 2015;46(3):807-18. doi: 10.1183/13993003.02139-2014
Go to original source... - Xie N, Liu G. ncRNA-regulated immune response and its role in inflammatory lung diseases. Am J Physiol Lung Cell Mol Physiol 2015;309(10):L1076-87. doi: 10.1152/ajplung.00286.2015
Go to original source...
Go to PubMed... - Leidinger P, Keller A, Borries A, Huwer H, Rohling M, Huebers J, Lenhof HP, Meese E. Specific peripheral miRNA profiles for distinguishing lung cancer from COPD. Lung cancer 2011;74(1):41-7. doi: 10.1016/j.lungcan.2011.02.003
Go to original source...
Go to PubMed... - Sai XY, Qin C, Zhang ZX, Yu HD, Bian T. A miRNA-21-Mediated PTEN/Akt/NF-κB Axis Promotes Chronic Obstructive Pulmonary Disease Pathogenesis. Int J Chron Obstruct Pulmon Dis 2024;19:1141-51. doi: 10.2147/COPD.S453593
Go to original source...
Go to PubMed... - Nadi E, Geramirad G, Kahramfar Z, Rasuli-Saravani A, Solgi G. Peripheral Blood Expressions of MicroRNA-146a and MicroRNA-218 in Chronic Obstructive Pulmonary Disease with/without Cigarette Smoke Exposure. Iran J Allergy Asthma Immunol 2022;21(4):399-406. doi: 10.18502/ijaai.v21i4.10287
Go to original source... - Roffel MP, Maes T, Brandsma CA, van den Berge M, Vanaudenaerde BM, Joos GF, Brusselle GG, Heijink IH, Bracke KR. MiR-223 is increased in lungs of patients with COPD and modulates cigarette smoke-induced pulmonary inflammation. Am J Physiol Lung Cell Mol Physiol 2021;321(6):L1091-l104. doi: 10.1152/ajplung.00252.2021
Go to original source... - Liu M, Wang YQ, Lu HF, Wang H, Shi XM, Shao X, Li YX, Zhao YY, Wang YL. miR-518b Enhances Human Trophoblast Cell Proliferation Through Targeting Rap1b and Activating Ras-MAPK Signal. Front Endocrinol (Lausanne) 2018;9:100. doi: 10.3389/fendo.2018.00100
Go to original source...
Go to PubMed... - Yang WM, Lu ZY, Zhi ZF, Liu LL, Deng LJ, Jiang XL, Pang LH. Increased miRNA-518b inhibits trophoblast migration and angiogenesis by targeting EGR1 in early embryonic arrest†. Biol Reprod 2019;101(4):664-74. doi: 10.1093/biolre/ioz109
Go to original source...
Go to PubMed... - Zhang Y, Hou HY, Sui WW, Liu YM, Zeng QL, Li YY, Li C, Zhou H, Zhang YM. Impact of ATP Synthase Subunit β on TLR Signaling Pathway in Promoting Airway Remodeling and Heterogeneity of Small Airway Epithelial Cells in Chronic Obstructive Pulmonary Disease. J Innate Immun 2025;17(1):1-27. doi: 10.1159/000547329
Go to original source...
Go to PubMed... - Yeh LY, Fang YT, Lee HS, Liu CH, Chen YY, Lo YC, Laiman V, Liou JP, Chung KF, Chuang HC, Lin CH. A Potent Histone Deacetylase Inhibitor MPT0E028 Mitigates Emphysema Severity via Components of the Hippo Signaling Pathway in an Emphysematous Mouse Model. Front Med (Lausanne) 2022;9:794025. doi: 10.3389/fmed.2022.794025
Go to original source... - Sabroe I, Whyte MK. Toll-like receptor (TLR)-based networks regulate neutrophilic inflammation in respiratory disease. Biochem Soc Trans 2007;35(Pt 6):1492-5. doi: 10.1042/BST0351492
Go to original source...
Go to PubMed... - Tang WF, Li M, Yangzhong XT, Zhang XF, Zu AJ, Hou YJ, Li L, Sun, SB. Hippo signaling pathway and respiratory diseases. Cell Death Discov 2022;8(1):213. doi: 10.1038/s41420-022-01020-6
Go to original source... - Xie LH, Wu MH, Lin H, Liu C, Yang HH, Zhan J, Sun SH. An increased ratio of serum miR-21 to miR-181a levels is associated with the early pathogenic process of chronic obstructive pulmonary disease in asymptomatic heavy smokers. Mol Biosyst 2014;10(5):1072-81. doi: 10.1039/c3mb70564a
Go to original source...
Go to PubMed... - Velasco-Torres Y, Ruiz-López V, Pérez-Bautista O, Buendía-Roldan I, Ramírez-Venegas A, Pérez-Ramos J, Falfán-Valencia R, Ramos C, Montaño M. miR-34a in serum is involved in mild-to-moderate COPD in women exposed to biomass smoke. BMC Pulm Med 2019;19(1):227. doi: 10.1186/s12890-019-0977-5
Go to original source...
Go to PubMed... - Chatila WM, Criner GJ, Hancock WW, Akimova T, Moldover B, Chang JK, Cornwell W, Santerre M, Rogers TJ. Blunted expression of miR-199a-5p in regulatory T cells of patients with chronic obstructive pulmonary disease compared to unaffected smokers. Clin Exp Immunol 2014;177(1):341-52. doi: 10.1111/cei.12325
Go to original source...
Go to PubMed...
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