Current issue
Archive
Manuscripts accepted
About the Journal
Editorial office
Editorial board
Abstracting and indexing
Subscription
Contact
Ethical standards and procedures
Most read articles
Instructions for authors
Article Processing Charge (APC)
Regulations of paying article processing charge (APC)
PULMONOLOGY / BASIC RESEARCH
Identifying potential molecular markers and therapeutic targets for chronic obstructive pulmonary disease using transcriptome sequencing and gene expression chip technology
1
Department of Respiratory and Critical Care, First Hospital of Hebei Medical University, Shijiazhuang City, Hebei Province, China
2
Respiratory Medicine, Jiyang District People’s Hospital, Jiyang District, Jinan, Shandong Province, China
3
Department of Respiratory and Critical Care Medicine, Liaocheng People’s Hospital, Liaocheng City, China
4
Department of Geriatrics, First Hospital of Hebei Medical University, Shijiazhuang City, Hebei Province, China
Submission date: 2024-03-04
Final revision date: 2024-07-18
Acceptance date: 2024-07-31
Online publication date: 2024-09-07
Corresponding author
Lindong Yuan
Department of Respiratory and Critical Care Medicine, Liaocheng People's Hospital, No.67, Dongchang West Road, Liaocheng City, 252000, China., Liaocheng, China
Department of Respiratory and Critical Care Medicine, Liaocheng People's Hospital, No.67, Dongchang West Road, Liaocheng City, 252000, China., Liaocheng, China
KEYWORDS
TOPICS
ABSTRACT
Introduction:
Chronic obstructive pulmonary disease (COPD) is a progressive lung disorder characterized by persistent respiratory symptoms and progressive airflow obstruction. The global rise in COPD incidence and mortality imposes a significant societal burden. Despite its prevalence, the intricate pathogenesis of COPD remains incompletely understood. This study aimed to identify molecular markers and potential therapeutic targets by integrating known COPD-related genes and analyzing RNA-Seq and expression microarray data.
Material and methods:
We conducted a comprehensive analysis by combining RNA-Seq and expression microarray data for COPD, focusing on known COPD-associated genes. Differential expression analysis revealed insights into the cellular biological processes and signaling pathways underlying COPD pathogenesis. Functional modules closely linked to COPD were identified through protein interaction network analysis.
Results:
The analysis of differentially expressed genes (DEGs) highlighted the significance of cellular processes such as chemotaxis, cell migration, cellular stress, and apoptosis in COPD pathogenesis. Key signaling pathways, including NF-B, JAK-STAT, T cell receptor, and NOD-like receptor pathways, were identified as crucial contributors to COPD development. Protein interaction network analysis revealed functional modules associated with COPD. Validation through qRT-PCR and immunoblotting confirmed PTX3 and CYP1B1 as core genes, suggesting their potential as biomarkers and therapeutic targets for COPD.
Conclusions:
Our findings provide valuable insights into the molecular landscape of COPD, identifying PTX3 and CYP1B1 as promising candidates for further investigation as potential biomarkers and therapeutic targets. This research contributes to a better understanding of COPD pathogenesis, offering avenues for the development of targeted interventions to address this escalating global health concern.
Chronic obstructive pulmonary disease (COPD) is a progressive lung disorder characterized by persistent respiratory symptoms and progressive airflow obstruction. The global rise in COPD incidence and mortality imposes a significant societal burden. Despite its prevalence, the intricate pathogenesis of COPD remains incompletely understood. This study aimed to identify molecular markers and potential therapeutic targets by integrating known COPD-related genes and analyzing RNA-Seq and expression microarray data.
Material and methods:
We conducted a comprehensive analysis by combining RNA-Seq and expression microarray data for COPD, focusing on known COPD-associated genes. Differential expression analysis revealed insights into the cellular biological processes and signaling pathways underlying COPD pathogenesis. Functional modules closely linked to COPD were identified through protein interaction network analysis.
Results:
The analysis of differentially expressed genes (DEGs) highlighted the significance of cellular processes such as chemotaxis, cell migration, cellular stress, and apoptosis in COPD pathogenesis. Key signaling pathways, including NF-B, JAK-STAT, T cell receptor, and NOD-like receptor pathways, were identified as crucial contributors to COPD development. Protein interaction network analysis revealed functional modules associated with COPD. Validation through qRT-PCR and immunoblotting confirmed PTX3 and CYP1B1 as core genes, suggesting their potential as biomarkers and therapeutic targets for COPD.
Conclusions:
Our findings provide valuable insights into the molecular landscape of COPD, identifying PTX3 and CYP1B1 as promising candidates for further investigation as potential biomarkers and therapeutic targets. This research contributes to a better understanding of COPD pathogenesis, offering avenues for the development of targeted interventions to address this escalating global health concern.
REFERENCES (53)
1.
Barnes PJ, Burney PG, Silverman EK, Celli BR, Vestbo J, Wedzicha JA, et al. Chronic obstructive pulmonary disease. Nat Rev Dis Primers 2015; 1: 15076.
2.
Ruvuna L, Sood A. Epidemiology of chronic obstructive pulmonary disease. Clin Chest Med 2020; 41: 315-27.
3.
Yang IA, Jenkins CR, Salvi SS. Chronic obstructive pulmonary disease in never-smokers: risk factors, pathogenesis, and implications for prevention and treatment. Lancet Respir Med 2022; 10: 497-511.
4.
Chen X, Zhou CW, Fu YY, et al. Global, regional, and national burden of chronic respiratory diseases and associated risk factors, 1990-2019: Results from the Global Burden of Disease Study 2019. Front Med (Lausanne) 2023; 10: 1066804.
5.
Lopez-Campos JL, Tan W, Soriano JB. Global burden of COPD. Respirology 2016; 21: 14-23.
6.
Viegi G, Maio S, Fasola S, Baldacci S. Global burden of chronic respiratory diseases. J Aerosol Med Pulm Drug Deliv 2020; 33: 171-7.
7.
Burney P, Jarvis D, Perez-Padilla R. The global burden of chronic respiratory disease in adults. Int J Tuberc Lung Dis 2015; 19: 10-20.
8.
Vogelmeier CF, Roman-Rodriguez M, Singh D, Han MK, Rodriguez-Roisin R, Ferguson GT. Goals of COPD treatment: focus on symptoms and exacerbations. Respir Med 2020; 166: 105938.
9.
Nici L, Mammen MJ, Charbek E, et al. Pharmacologic management of chronic obstructive pulmonary disease. An Official American Thoracic Society Clinical Practice Guideline Am J Respir Crit Care Med 2020; 201: e56-e69. doi: 10.1164/rccm.202003-0625ST. Erratum in: Am J Respir Crit Care Med 2020; 202: 910. doi: 10.1164/rccm.v202erratum5.
10.
Dang X, He B, Ning Q, et al. Alantolactone suppresses inflammation, apoptosis and oxidative stress in cigarette smoke-induced human bronchial epithelial cells through activation of Nrf2/HO-1 and inhibition of the NF-kappaB pathways. Respir Res 2020; 21: 95.
11.
Zhang MY, Jiang YX, Yang YC, et al. Cigarette smoke extract induces pyroptosis in human bronchial epithelial cells through the ROS/NLRP3/caspase-1 pathway. Life Sci 2021; 269: 119090.
12.
Wang Z, Locantore N, Haldar K, et al. Inflammatory endotype-associated airway microbiome in chronic obstructive pulmonary disease clinical stability and exacerbations: a multicohort longitudinal analysis. Am J Respir Crit Care Med 2021; 203: 1488-502.
13.
Kim HT, Yin W, Nakamichi Y, et al. WNT/RYK signaling restricts goblet cell differentiation during lung development and repair. Proc Natl Acad Sci USA 2019; 116: 25697-706.
14.
Mojiri-Forushani H, Hemmati AA, Khodadadi A, Rashno M. Valsartan attenuates bleomycin-induced pulmonary fibrosis by inhibition of NF-kappaB expression and regulation of Th1/Th2 cytokines. Immunopharmacol Immunotoxicol 2018; 40: 225-31.
15.
Guo L, Li N, Yang Z, et al. Role of CXCL5 in regulating chemotaxis of innate and adaptive leukocytes in infected lungs upon pulmonary influenza infection. Front Immunol 2021; 12: 785457. doi: 10.3389/fimmu.2021.785457.
16.
Keranen T, Moilanen E, Korhonen R. Suppression of cytokine production by glucocorticoids is mediated by MKP-1 in human lung epithelial cells. Inflamm Res 2017; 66: 441-9.
17.
Brusselle GG, Joos GF, Bracke KR. New insights into the immunology of chronic obstructive pulmonary disease. Lancet 2011; 378: 1015-26. doi: 10.1016/S0140-6736(11)60988-4.
18.
Jeong I, Lim JH, Oh DK, Kim WJ, Oh YM. Gene expression profile of human lung in a relatively early stage of COPD with emphysema. Int J Chron Obstruct Pulmon Dis 2018; 13: 2643-55.
19.
Fathinavid A, Ghobadi MZ, Najafi A, Masoudi-Nejad A. Identification of common microRNA between COPD and non-small cell lung cancer through pathway enrichment analysis. BMC Genom Data 2021; 22: 41. doi: 10.1186/s12863-021-00986-z.
20.
Regan EA, Hersh CP, Castaldi PJ, et al. Omics and the search for blood biomarkers in chronic obstructive pulmonary disease. Insights from COPDGene. Am J Respir Cell Mol Biol 2019; 61: 143-9.
21.
Szklarczyk D, Kirsch R, Koutrouli M, et al. The STRING database in 2023: protein-protein association networks and functional enrichment analyses for any sequenced genome of interest. Nucleic Acids Res 2023; 51: D638-D46.
22.
Trapnell C, Roberts A, Goff L, et al. Differential gene and transcript expression analysis of RNA-seq experiments with TopHat and Cufflinks. Nat Protoc 2012; 7: 562-78. Erratum in: Nat Protoc 2014; 9: 2513.
23.
Ritchie ME, Phipson B, Wu D, et al. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res 2015; 43: e47. doi: 10.1093/nar/gkv007.
24.
Wickham H. ggplot2: Elegant Graphics for Data Analysis. Springer-Verlag, New York 2016.
25.
Yu G, Wang LG, Han Y, He QY. clusterProfiler: an R package for comparing biological themes among gene clusters. OMICS 2012; 16: 284-7.
26.
Pinero J, Sauch J, Sanz F, Furlong LI. The DisGeNET cytoscape app: exploring and visualizing disease genomics data. Comput Struct Biotechnol J 2021; 19: 2960-7.
27.
Shannon P, Markiel A, Ozier O, et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res 2003; 13: 2498-504.
28.
Chin CH, Chen SH, Wu HH, Ho CW, Ko MT, Lin CY. cytoHubba: identifying hub objects and sub-networks from complex interactome. BMC Syst Biol 2014; 8 Suppl 4: S11.
29.
Duffy SP, Criner GJ. Chronic obstructive pulmonary disease: evaluation and management. Med Clin North Am 2019; 103: 453-61.
30.
Christenson SA, Smith BM, Bafadhel M, Putcha N. Chronic obstructive pulmonary disease. Lancet 2022; 399: 2227-42.
31.
Duan JX, Cheng W, Zeng YQ, et al. Characteristics of patients with chronic obstructive pulmonary disease exposed to different environmental risk factors: a large cross-sectional study. Int J Chron Obstruct Pulmon Dis 2020; 15: 2857-67.
32.
Salvi S. Tobacco smoking and environmental risk factors for chronic obstructive pulmonary disease. Clin Chest Med 2014; 35: 17-27.
33.
Kuang LJ, Deng TT, Wang Q, et al. Dendritic cells induce Tc1 cell differentiation via the CD40/CD40L pathway in mice after exposure to cigarette smoke. Am J Physiol Lung Cell Mol Physiol 2016; 311: L581-9.
34.
Lin YZ, Zhong XN, Chen X, Liang Y, Zhang H, Zhu DL. Roundabout signaling pathway involved in the pathogenesis of COPD by integrative bioinformatics analysis. Int J Chron Obstruct Pulmon Dis 2019; 14: 2145-62.
35.
Huang X, Li Y, Guo X, et al. Identification of differentially expressed genes and signaling pathways in chronic obstructive pulmonary disease via bioinformatic analysis. FEBS Open Bio 2019; 9: 1880-99.
36.
Li Q, Wang C, Wang Y, et al. HSCs-derived COMP drives hepatocellular carcinoma progression by activating MEK/ERK and PI3K/AKT signaling pathways. J Exp Clin Cancer Res 2018; 37: 231.
37.
Butler A, Walton GM, Sapey E. Neutrophilic inflammation in the pathogenesis of chronic obstructive pulmonary disease. COPD 2018; 15: 392-404.
38.
Liu J, Zhong X, He Z, et al. Erythromycin suppresses the cigarette smoke extract-exposed dendritic cell-mediated polarization of CD4+ T cells into Th17 cells. J Immunol Res 2020; 2020: 1387952. doi: 10.1155/2020/1387952.
39.
Yi X, Li Y, Liu H, et al. Inflammatory endotype-associated airway resistome in chronic obstructive pulmonary disease. Microbiol Spectr 2022; 10: e0259321. doi: 10.1128/spectrum.02593-21.
40.
De Cunto G, Cavarra E, Bartalesi B, Lucattelli M, Lungarella G. Innate immunity and cell surface receptors in the pathogenesis of COPD: insights from mouse smoking models. Int J Chron Obstruct Pulmon Dis 2020; 15: 1143-54.
41.
Al Saedi A, Sharma S, Bani Hassan E, et al. Characterization of skeletal phenotype and associated mechanisms with chronic intestinal inflammation in the winnie mouse model of spontaneous chronic colitis. Inflamm Bowel Dis 2022; 28: 259-72. doi: 10.1093/ibd/izab174.
42.
Liu X, Li L, Wang Q, et al. A novel humanized anti-interleukin-6 antibody HZ0408b with anti-rheumatoid arthritis therapeutic potential. Front Immunol 2022; 12: 816646. doi: 10.3389/fimmu.2021.816646.
43.
Van Damme J, De Ley M, Opdenakker G, Billiau A, De Somer P, Van Beeumen J. Homogeneous interferon-inducing 22K factor is related to endogenous pyrogen and interleukin-1. Nature 1985; 314: 266-8.
44.
Rackov G, Tavakoli Zaniani P, Colomo Del Pino S, et al. Mitochondrial reactive oxygen is critical for IL-12/IL-18-induced IFN-γ production by CD4+ T cells and is regulated by Fas/FasL signaling. Cell Death Dis 2022; 13: 531.
45.
Slusher AL, Mischo AB, Acevedo EO. Pentraxin 3 is an anti-inflammatory protein associated with lipid-induced interleukin 10 in vitro. Cytokine 2016; 86: 36-40.
46.
Maccarinelli F, Bugatti M, Churruca Schuind A, et al. Endogenous long pentraxin 3 exerts a protective role in a murine model of pulmonary fibrosis. Front Immunol 2021; 12: 617671. doi: 10.3389/fimmu.2021.617671.
47.
Kim HS, Moon SJ, Lee SE, Hwang GW, Yoo HJ, Song JW. The arachidonic acid metabolite 11,12-epoxyeicosatrienoic acid alleviates pulmonary fibrosis. Exp Mol Med 2021; 53: 864-74.
48.
Kwon YJ, Shin S, Chun YJ. Biological roles of cytochrome P450 1A1, 1A2, and 1B1 enzymes. Arch Pharm Res 2021; 44: 63-83.
49.
Kaur-Knudsen D, Bojesen SE, Nordestgaard BG. Cytochrome P450 1B1 and 2C9 genotypes and risk of ischemic vascular disease, cancer, and chronic obstructive pulmonary disease. Curr Vasc Pharmacol 2012; 10: 512-20.
50.
Morrow JD, Chase RP, Parker MM, et al. RNA-sequencing across three matched tissues reveals shared and tissue-specific gene expression and pathway signatures of COPD. Respir Res 2019; 20: 65.
51.
Kamata S, Fujino N, Yamada M, et al. Expression of cytochrome P450 mRNAs in type II alveolar cells from subjects with chronic obstructive pulmonary disease. Pharmacol Res Perspect 2018; 6: e00405. doi: 10.1002/prp2.405.
52.
Kurt OK, Tosun M, Kurt EB, Talay F. Pentraxin 3 as a novel biomarker of inflammation in chronic obstructive pulmonary disease. Inflammation 2015; 38: 89-93.
53.
Duran L, Unsal M, Yardan T, et al. The evaluation of serum pentraxin-3 and high-sensitivity C-reactive protein levels in patients with acute attack of COPD. Clin Lab 2015; 61: 1911-6.
Share
RELATED ARTICLE
| eISSN: | 1896-9151 |
| ISSN: | 1734-1922 |
We process personal data collected when visiting the website. The function of obtaining information about users and their behavior is carried out by voluntarily entered information in forms and saving cookies in end devices. Data, including cookies, are used to provide services, improve the user experience and to analyze the traffic in accordance with the Privacy policy. Data are also collected and processed by Google Analytics tool (more).
You can change cookies settings in your browser. Restricted use of cookies in the browser configuration may affect some functionalities of the website.
You can change cookies settings in your browser. Restricted use of cookies in the browser configuration may affect some functionalities of the website.
