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N6\u2010methyladenosine (m6A) modifications regulate gene expression and various facets of cancer biology; nonetheless, the mechanisms by which they modulate gene expression in TAMs and their impact on LUAD progression remain inadequately elucidated. Single\u2010cell transcriptome analysis identified the macrophage m6A\u2010related genes (MMRGs) with high expression in TAMs and linked to m6A modifications in LUAD. The MMRGs were employed to construct 801 prognostic models by 13 different machine learning (ML) algorithms. An integrative multi\u2010omics approach was utilized to analyze the potential biological functions of MMRGs. Five ML algorithms were employed to discover potential biomarkers for patient stratification and precision therapy. Potential drugs for treating LUAD were identified and assessed by molecular docking and molecular dynamics, and ML was employed to determine the most promising candidates. Immunohistochemistry and immunofluorescence staining were conducted to assess MMRG expression in LUAD tissues. Seventeen MMRGs were identified in LUAD and subsequently employed to construct a prognostic model for patient stratification into high\u2010risk and low\u2010risk groups. The impact of MMRG expression on various tumor immune phenotypes, such as tumor stemness, heterogeneity, hallmark pathway enrichment, TAM infiltration, and immune landscape, was thoroughly characterized.\n                    <jats:italic>PIM3<\/jats:italic>\n                    ,\n                    <jats:italic>HMGB2<\/jats:italic>\n                    ,\n                    <jats:italic>DUSP2<\/jats:italic>\n                    ,\n                    <jats:italic>NR4A2<\/jats:italic>\n                    , and others were recognized as promising biomarkers for patient classification and precision therapy. Furthermore, it was predicted that drugs such as BRD9876 and MK\u20101775 would demonstrate therapeutic efficacy in treating LUAD, and drugs showing potential binding with DUSP2, ZNF331, FLT, and LYZ were identified. Finally, experimental validation was conducted to confirm the protein expression and distribution of DUSP2 and NR4A2 in tissues of LUAD. Our study offers valuable insights into the biological significance of MMRGs, shedding light on novel mechanisms of tumor development and immune evasion in LUAD. Furthermore, our findings have identified potential biomarkers, drug candidates, and therapeutic targets that may improve the management of LUAD in the future.\n                  <\/jats:p>","DOI":"10.1096\/fj.202500293rr","type":"journal-article","created":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T02:41:17Z","timestamp":1749177677000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Characterization of\n                    <scp>m6A<\/scp>\n                    \u2010Related Genes in Tumor\u2010Associated Macrophages for Prognosis, Immunotherapy, and Drug Prediction in Lung Adenocarcinomas Based on Machine Learning Algorithms"],"prefix":"10.1096","volume":"39","author":[{"given":"Mengmeng","family":"Sang","sequence":"first","affiliation":[{"name":"Department of Immunology, School of Medicine Nantong University  Nantong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinhua","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Immunology, School of Medicine Nantong University  Nantong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mimi","family":"Mao","sequence":"additional","affiliation":[{"name":"Department of Radiology Nantong Tumor Hospital Affiliated to Nantong University  Nantong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoming","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Immunology, School of Medicine Nantong University  Nantong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Ge","sequence":"additional","affiliation":[{"name":"Department of Immunology, School of Medicine Nantong University  Nantong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine Affiliated Hospital of Nantong University  Nantong Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenhao","family":"Ju","sequence":"additional","affiliation":[{"name":"Department of Structural Heart Disease, National Center for Cardiovascular Disease, China and Fuwai Hospital Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaorong","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Immunology, School of Medicine Nantong University  Nantong China"},{"name":"Jiangsu Province Key Laboratory in University for Inflammation and Molecular Drug Target Nantong University  Nantong China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,6,5]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-017-0063-y"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-018-0081-9"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.802080"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-021-01411-w"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2021.121137"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-020-00983-2"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-023-01452-1"},{"key":"e_1_2_12_9_1","article-title":"Much More Than M1 and M2 Macrophages, There Are Also CD169(+) and TCR(+) Macrophages","volume":"6","author":"Chavez\u2010Galan L.","year":"2015","journal-title":"Frontiers in Immunology"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.867260"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2023.1061353"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/s10020-024-00866-z"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25042407"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41698-024-00522-z"},{"issue":"6","key":"e_1_2_12_15_1","first-page":"4490","article-title":"M2 Tumor\u2010Associated Macrophages Promote Tumor Progression in Non\u2010Small\u2010Cell Lung Cancer","volume":"18","author":"Sumitomo R.","year":"2019","journal-title":"Experimental and Therapeutic Medicine"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep14273"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11033-022-07329-w"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/burnst\/tkaa006"},{"issue":"3","key":"e_1_2_12_19_1","doi-asserted-by":"crossref","DOI":"10.1136\/jitc-2022-006433","article-title":"Invasive Margin Tissue\u2010Resident Macrophages of High CD163 Expression Impede Responses to T Cell\u2010Based Immunotherapy","volume":"11","author":"Elsas M. 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