{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T15:35:41Z","timestamp":1789054541987,"version":"build-2803163510"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T00:00:00Z","timestamp":1672790400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007847","name":"Natural Science Foundation of Jilin Province","doi-asserted-by":"publisher","award":["YDZJ202201ZYTS188"],"award-info":[{"award-number":["YDZJ202201ZYTS188"]}],"id":[{"id":"10.13039\/100007847","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p>\n                    <jats:bold>Introduction:<\/jats:bold>\n                    Idiopathic pulmonary fibrosis (IPF) is a chronic progressive pulmonary fibrotic disease with unknown etiology and poor outcomes. It severely affects the quality of life. In this study, we comprehensively analyzed the expression of N6-methyladenosine (m6A) RNA methylation regulators using gene expression data from various tissue sources in IPF patients and healthy volunteers.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Methods:<\/jats:bold>\n                    The gene expression matrix and clinical characteristics of IPF patients were retrieved from the Gene Expression Omnibus database. A random forest model was used to construct diagnosis signature m6A regulators. Regression analysis and correlation analysis were used to identify prognosis m6A regulators. Consensus cluster analysis was used to construct different m6A prognosis risk groups, then functional enrichment, immune infiltration and drug sensitivity analysis were performed.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Result:<\/jats:bold>\n                    Five candidate m6A genes from lung tissue were used to predict the incidence, and the incidence was validated using datasets from bronchoalveolar lavage fluid (BALF) and peripheral blood mononuclear cells. Subsequently, the BALF dataset containing outcomes data was used for the prognosis analysis of m6A regulators.\n                    <jats:italic>METTL14<\/jats:italic>\n                    ,\n                    <jats:italic>G3BP2<\/jats:italic>\n                    , and\n                    <jats:italic>ZC3H13<\/jats:italic>\n                    were independent protective factors. Using correlation analysis with lung function in the lung tissue-derived dataset,\n                    <jats:italic>METTL14<\/jats:italic>\n                    was a protective factor in IPF. Based on\n                    <jats:italic>METTL14<\/jats:italic>\n                    and\n                    <jats:italic>G3BP2<\/jats:italic>\n                    , a consensus cluster analysis was applied to distinguish the prognostic m6A regulation patterns. The low-risk group\u2019s prognosis was significantly better than the high-risk group. Biological processes regulated by various risk groups included fibrogenesis and cell adhesion. Analysis of immune cell infiltration showed upregulation of neutrophils in the m6A high-risk group. Subsequently, five m6A high-risk group sensitive drugs and one m6A low-risk group sensitive drug were identified.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Discussion:<\/jats:bold>\n                    These findings suggest that m6A regulators are involved in the diagnosis and prognosis of IPF, and m6A patterns are a method to identify IPF outcomes.\n                  <\/jats:p>","DOI":"10.3389\/fgene.2022.1102422","type":"journal-article","created":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T12:09:16Z","timestamp":1672834156000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Genes related to N6-methyladenosine in the diagnosis and prognosis of idiopathic pulmonary fibrosis"],"prefix":"10.3389","volume":"13","author":[{"given":"Jingcheng","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyuan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiachao","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenyu","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keju","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baojin","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qibiao","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,1,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e000899","DOI":"10.1136\/bmjresp-2021-000899","article-title":"Monocyte and neutrophil levels are potentially linked to progression to IPF for patients with indeterminate UIP CT pattern","volume":"8","author":"Achaiah","year":"2021","journal-title":"BMJ Open Respir. Res."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1340","DOI":"10.1093\/bioinformatics\/btq134","article-title":"Permutation importance: A corrected feature importance measure","volume":"26","author":"Altmann","year":"2010","journal-title":"Bioinformatics"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1128","DOI":"10.1038\/s41591-018-0090-y","article-title":"Reducing protein oxidation reverses lung fibrosis","volume":"24","author":"Anathy","year":"2018","journal-title":"Nat. Med."},{"key":"B4","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1038\/75556","article-title":"Gene ontology: Tool for the unification of biology. The gene Ontology consortium","volume":"25","author":"Ashburner","year":"2000","journal-title":"Nat. Genet."},{"key":"B5","doi-asserted-by":"publisher","first-page":"17697","DOI":"10.1016\/s0021-9258(17)32497-3","article-title":"Characterization and partial purification of mRNA N6-adenosine methyltransferase from HeLa cell nuclei. Internal mRNA methylation requires a multisubunit complex","volume":"269","author":"Bokar","year":"1994","journal-title":"J. Biol. Chem."},{"key":"B6","doi-asserted-by":"publisher","first-page":"3631","DOI":"10.3390\/ijms23073631","article-title":"Pirfenidone sensitizes NCI-H460 non-small cell lung cancer cells to paclitaxel and to a combination of paclitaxel with carboplatin","volume":"23","author":"Branco","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"B7","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1016\/j.mam.2018.08.004","article-title":"Developmental pathways in the pathogenesis of lung fibrosis","volume":"65","author":"Chanda","year":"2019","journal-title":"Mol. Asp. Med."},{"key":"B8","doi-asserted-by":"publisher","first-page":"882217","DOI":"10.3389\/fimmu.2022.882217","article-title":"Prognostic role of NLR, PLR and MHR in patients with idiopathic pulmonary fibrosis","volume":"13","author":"Chen","year":"2022","journal-title":"Front. Immunol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1902058","DOI":"10.1183\/13993003.02058-2019","article-title":"Circulating RNA differences between patients with stable and progressive idiopathic pulmonary fibrosis","volume":"59","author":"Clynick","year":"2022","journal-title":"Eur. Respir. J."},{"key":"B10","doi-asserted-by":"publisher","first-page":"526","DOI":"10.23736\/S0026-4806.20.06614-8","article-title":"Neutrophil-to-lymphocyte ratio in bronchoalveolar lavage from IPF patients: A novel prognostic biomarker?","volume":"113","author":"D'Alessandro","year":"2022","journal-title":"Minerva Med."},{"key":"B11","doi-asserted-by":"publisher","first-page":"404","DOI":"10.1016\/j.matbio.2018.01.023","article-title":"Biomarkers in idiopathic pulmonary fibrosis","author":"Drakopanagiotakis","year":"2018","journal-title":"Matrix Biol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"679367","DOI":"10.3389\/fonc.2021.679367","article-title":"m6A modification: A double-edged sword in tumor development","volume":"11","author":"Gao","year":"2021","journal-title":"Front. Oncol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"D325","DOI":"10.1093\/nar\/gkaa1113","article-title":"The gene ontology resource: Enriching a GOld mine","volume":"49","author":"Gene Ontology","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"B14","doi-asserted-by":"publisher","first-page":"205ra136","DOI":"10.1126\/scitranslmed.3005964","article-title":"Peripheral blood mononuclear cell gene expression profiles predict poor outcome in idiopathic pulmonary fibrosis","volume":"5","author":"Herazo-Maya","year":"2013","journal-title":"Sci. Transl. Med."},{"key":"B15","doi-asserted-by":"publisher","first-page":"e225","DOI":"10.6061\/clinics\/2019\/e225","article-title":"Imaging in idiopathic pulmonary fibrosis: Diagnosis and mimics","volume":"74","author":"Hochhegger","year":"2019","journal-title":"Clin. (Sao Paulo)"},{"key":"B16","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1186\/s12890-015-0142-8","article-title":"A functional genomic model for predicting prognosis in idiopathic pulmonary fibrosis","volume":"15","author":"Huang","year":"2015","journal-title":"BMC Pulm. Med."},{"key":"B17","doi-asserted-by":"publisher","first-page":"917973","DOI":"10.3389\/fmed.2022.917973","article-title":"IPF respiratory symptoms management - current evidence","volume":"9","author":"Janowiak","year":"2022","journal-title":"Front. Med. (Lausanne)"},{"key":"B18","doi-asserted-by":"publisher","first-page":"945","DOI":"10.3904\/kjim.2022.267","article-title":"The role of neutrophils in the pathogenesis of IPF","volume":"37","author":"Jegal","year":"2022","journal-title":"Korean J. Intern Med."},{"key":"B19","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1038\/s41392-020-00450-x","article-title":"The role of m6A modification in the biological functions and diseases","volume":"6","author":"Jiang","year":"2021","journal-title":"Signal Transduct. Target. Ther."},{"key":"B20","doi-asserted-by":"publisher","first-page":"e12124","DOI":"10.1002\/jev2.12124","article-title":"Human bronchial epithelial cell-derived extracellular vesicle therapy for pulmonary fibrosis via inhibition of TGF-beta-WNT crosstalk","volume":"10","author":"Kadota","year":"2021","journal-title":"J. Extracell. Vesicles"},{"key":"B21","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1093\/nar\/28.1.27","article-title":"Kegg: Kyoto encyclopedia of genes and genomes","volume":"28","author":"Kanehisa","year":"2000","journal-title":"Nucleic Acids Res."},{"key":"B22","doi-asserted-by":"publisher","first-page":"924","DOI":"10.1186\/s12864-015-2170-4","article-title":"Integrative phenotyping framework (iPF): Integrative clustering of multiple omics data identifies novel lung disease subphenotypes","volume":"16","author":"Kim","year":"2015","journal-title":"BMC Genomics"},{"key":"B23","doi-asserted-by":"publisher","first-page":"1285","DOI":"10.1158\/0008-5472.CAN-18-2965","article-title":"The critical role of RNA m(6)A methylation in cancer","volume":"79","author":"Lan","year":"2019","journal-title":"Cancer Res."},{"key":"B24","doi-asserted-by":"publisher","first-page":"3431","DOI":"10.1158\/0008-5472.CAN-20-4107","article-title":"The emerging roles of RNA m(6)A methylation and demethylation as critical regulators of tumorigenesis, drug sensitivity, and resistance","volume":"81","author":"Lan","year":"2021","journal-title":"Cancer Res."},{"key":"B25","doi-asserted-by":"publisher","first-page":"895","DOI":"10.1016\/j.humpath.2012.08.016","article-title":"Divergence of tight and adherens junction factors in alveolar epithelium in pulmonary fibrosis","volume":"44","author":"Lappi-Blanco","year":"2013","journal-title":"Hum. Pathol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1186\/s12943-022-01652-3","article-title":"Targeting RNA N(6)-methyladenosine modification: A precise weapon in overcoming tumor immune escape","volume":"21","author":"Li","year":"2022","journal-title":"Mol. Cancer"},{"key":"B27","doi-asserted-by":"publisher","first-page":"1074","DOI":"10.1038\/s41556-018-0174-4","article-title":"m(6 A mRNA methylation regulates AKT activity to promote the proliferation and tumorigenicity of endometrial cancer","volume":"20","author":"Liu","year":"2018","journal-title":"Nat. Cell Biol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"797292","DOI":"10.3389\/fphar.2021.797292","article-title":"Idiopathic pulmonary fibrosis: An update on pathogenesis","volume":"12","author":"Mei","year":"2021","journal-title":"Front. Pharmacol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"1427","DOI":"10.3390\/jcm10071427","article-title":"Changes in neutrophil-lymphocyte or platelet-lymphocyte ratios and their associations with clinical outcomes in idiopathic pulmonary fibrosis","volume":"10","author":"Nathan","year":"2021","journal-title":"J. Clin. Med."},{"key":"B30","doi-asserted-by":"publisher","first-page":"1565","DOI":"10.1038\/nbt1206-1565","article-title":"What is a support vector machine?","volume":"24","author":"Noble","year":"2006","journal-title":"Nat. Biotechnol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"4056","DOI":"10.1096\/fj.201600373R","article-title":"Plexin C1 deficiency permits synaptotagmin 7-mediated macrophage migration and enhances mammalian lung fibrosis","volume":"30","author":"Peng","year":"2016","journal-title":"FASEB J."},{"key":"B32","doi-asserted-by":"publisher","first-page":"622","DOI":"10.1164\/rccm.201712-2551OC","article-title":"BAL cell gene expression is indicative of outcome and airway basal cell involvement in idiopathic pulmonary fibrosis","volume":"199","author":"Prasse","year":"2019","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"B33","doi-asserted-by":"publisher","first-page":"8301888","DOI":"10.1155\/2022\/8301888","article-title":"m(6 A-related angiogenic genes to construct prognostic signature, reveal immune and oxidative stress landscape, and screen drugs in hepatocellular carcinoma","volume":"2022","author":"Qu","year":"2022","journal-title":"Oxid. Med. Cell Longev."},{"key":"B34","doi-asserted-by":"publisher","first-page":"L405","DOI":"10.1152\/ajplung.00143.2013","article-title":"Grainyhead-like 2 (GRHL2) distribution reveals novel pathophysiological differences between human idiopathic pulmonary fibrosis and mouse models of pulmonary fibrosis","volume":"306","author":"Varma","year":"2014","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"1388","DOI":"10.1016\/j.cell.2015.05.014","article-title":"N(6)-methyladenosine modulates messenger RNA translation efficiency","volume":"161","author":"Wang","year":"2015","journal-title":"Cell"},{"key":"B36","doi-asserted-by":"publisher","first-page":"420","DOI":"10.1038\/s41467-017-02770-z","article-title":"Molecular basis for the specific and multivariant recognitions of RNA substrates by human hnRNP A2\/B1","volume":"9","author":"Wu","year":"2018","journal-title":"Nat. Commun."},{"key":"B37","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1016\/j.molcel.2016.01.012","article-title":"Nuclear m(6)A reader YTHDC1 regulates mRNA splicing","volume":"61","author":"Xiao","year":"2016","journal-title":"Mol. Cell"},{"key":"B38","doi-asserted-by":"publisher","first-page":"608","DOI":"10.1038\/s41580-019-0168-5","article-title":"Reading, writing and erasing mRNA methylation","volume":"20","author":"Zaccara","year":"2019","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1186\/s13045-021-01173-4","article-title":"m(6 A regulators as predictive biomarkers for chemotherapy benefit and potential therapeutic targets for overcoming chemotherapy resistance in small-cell lung cancer","volume":"14","author":"Zhang","year":"2021","journal-title":"J. Hematol. Oncol."},{"key":"B40","doi-asserted-by":"publisher","first-page":"183205","DOI":"10.1016\/j.bbamem.2020.183205","article-title":"Idiopathic pulmonary fibrosis is associated with tight junction protein alterations","volume":"1862","author":"Zou","year":"2020","journal-title":"Biochim. Biophys. Acta Biomembr."}],"container-title":["Frontiers in Genetics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2022.1102422\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T12:09:20Z","timestamp":1672834160000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2022.1102422\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,4]]},"references-count":40,"alternative-id":["10.3389\/fgene.2022.1102422"],"URL":"https:\/\/doi.org\/10.3389\/fgene.2022.1102422","relation":{},"ISSN":["1664-8021"],"issn-type":[{"value":"1664-8021","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,4]]},"article-number":"1102422"}}