{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T10:51:17Z","timestamp":1791975077725,"version":"4.4.0"},"reference-count":41,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,7,19]],"date-time":"2026-07-19T00:00:00Z","timestamp":1784419200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:00:00Z","timestamp":1791936000000},"content-version":"vor","delay-in-days":87,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Discov Onc"],"DOI":"10.1007\/s12672-026-05569-x","type":"journal-article","created":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T23:55:12Z","timestamp":1784418912000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integration of network toxicology, machine learning and single-cell sequencing identifies candidate molecular links between air pollutants and hepatocellular carcinoma"],"prefix":"10.1007","volume":"17","author":[{"given":"Lin","family":"Yang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Qing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxing","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,19]]},"reference":[{"key":"5569_CR1","doi-asserted-by":"publisher","first-page":"S228","DOI":"10.3350\/cmh.2024.0824","volume":"31","author":"SY Hwang","year":"2025","unstructured":"Hwang SY, Danpanichkul P, Agopian V, et al. Hepatocellular carcinoma: Updates on epidemiology, surveillance, diagnosis and treatment. Clin Mol Hepatol. 2025;31:S228\u201354. https:\/\/doi.org\/10.3350\/cmh.2024.0824.","journal-title":"Clin Mol Hepatol"},{"key":"5569_CR2","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1186\/s40364-021-00319-3","volume":"9","author":"X Qing","year":"2021","unstructured":"Qing X, Xu W, Zong J, et al. Emerging treatment modalities for systemic therapy in hepatocellular carcinoma. Biomark Res. 2021;9:64. https:\/\/doi.org\/10.1186\/s40364-021-00319-3.","journal-title":"Biomark Res"},{"key":"5569_CR3","doi-asserted-by":"publisher","first-page":"766","DOI":"10.1053\/j.gastro.2023.01.033","volume":"164","author":"MR Toh","year":"2023","unstructured":"Toh MR, Wong EYT, Wong SH, et al. Global epidemiology and genetics of hepatocellular carcinoma. Gastroenterology. 2023;164:766\u201382. https:\/\/doi.org\/10.1053\/j.gastro.2023.01.033.","journal-title":"Gastroenterology"},{"key":"5569_CR4","doi-asserted-by":"publisher","first-page":"2972","DOI":"10.1186\/s12889-025-24162-5","volume":"25","author":"RM Odat","year":"2025","unstructured":"Odat RM, Hussain HAH, Alshwayyat S, et al. Global air pollution exposure and hepatocellular carcinoma: A systematic review and meta-analysis of epidemiological studies. BMC Public Health. 2025;25:2972. https:\/\/doi.org\/10.1186\/s12889-025-24162-5.","journal-title":"BMC Public Health"},{"key":"5569_CR5","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1002\/hep.21347","volume":"44","author":"R Williams","year":"2006","unstructured":"Williams R. Global challenges in liver disease. Hepatology. 2006;44:521\u20136. https:\/\/doi.org\/10.1002\/hep.21347.","journal-title":"Hepatology"},{"key":"5569_CR6","doi-asserted-by":"publisher","first-page":"e0627","DOI":"10.1097\/HC9.0000000000000627","volume":"9","author":"D Rayapati","year":"2025","unstructured":"Rayapati D, McGlynn KA, Groopman JD, Kim AK. Environmental exposures and the risk of hepatocellular carcinoma. Hepatol Commun. 2025;9:e0627. https:\/\/doi.org\/10.1097\/HC9.0000000000000627.","journal-title":"Hepatol Commun"},{"key":"5569_CR7","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1007\/s00204-020-02656-y","volume":"94","author":"S Canzler","year":"2020","unstructured":"Canzler S, Schor J, Busch W, et al. Prospects and challenges of multi-omics data integration in toxicology. Arch Toxicol. 2020;94:371\u201388. https:\/\/doi.org\/10.1007\/s00204-020-02656-y.","journal-title":"Arch Toxicol"},{"key":"5569_CR8","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1038\/s42003-021-01990-w","volume":"4","author":"R Mesnage","year":"2021","unstructured":"Mesnage R, Teixeira M, Mandrioli D, et al. Multi-omics phenotyping of the gut-liver axis reveals metabolic perturbations from a low-dose pesticide mixture in rats. Commun Biol. 2021;4:471. https:\/\/doi.org\/10.1038\/s42003-021-01990-w.","journal-title":"Commun Biol"},{"key":"5569_CR9","doi-asserted-by":"publisher","first-page":"152892","DOI":"10.1016\/j.tox.2021.152892","volume":"460","author":"D Lichtenstein","year":"2021","unstructured":"Lichtenstein D, Mentz A, Sprenger H, et al. A targeted transcriptomics approach for the determination of mixture effects of pesticides. Toxicology. 2021;460:152892. https:\/\/doi.org\/10.1016\/j.tox.2021.152892.","journal-title":"Toxicology"},{"key":"5569_CR10","doi-asserted-by":"publisher","first-page":"2888","DOI":"10.1038\/s41591-025-03929-8","volume":"31","author":"JS Ji","year":"2025","unstructured":"Ji JS, Dominici F, Gouveia N, et al. Air pollution interventions for health. Nat Med. 2025;31:2888\u2013900. https:\/\/doi.org\/10.1038\/s41591-025-03929-8.","journal-title":"Nat Med"},{"key":"5569_CR11","doi-asserted-by":"publisher","first-page":"111487","DOI":"10.1016\/j.envres.2021.111487","volume":"201","author":"FH Dominski","year":"2021","unstructured":"Dominski FH, Lorenzetti Branco JH, Buonanno G, et al. Effects of air pollution on health: A mapping review of systematic reviews and meta-analyses. Environ Res. 2021;201:111487. https:\/\/doi.org\/10.1016\/j.envres.2021.111487.","journal-title":"Environ Res"},{"key":"5569_CR12","doi-asserted-by":"publisher","first-page":"560","DOI":"10.1016\/j.jhep.2024.09.033","volume":"82","author":"S Ran","year":"2025","unstructured":"Ran S, Zhang J, Tian F, et al. Association of metabolic signatures of air pollution with MASLD: Observational and mendelian randomization study. J Hepatol. 2025;82:560\u201370. https:\/\/doi.org\/10.1016\/j.jhep.2024.09.033.","journal-title":"J Hepatol"},{"key":"5569_CR13","doi-asserted-by":"publisher","first-page":"o1664","DOI":"10.1136\/bmj.o1664","volume":"378","author":"S Holgate","year":"2022","unstructured":"Holgate S. Air pollution is a public health emergency. BMJ. 2022;378:o1664. https:\/\/doi.org\/10.1136\/bmj.o1664.","journal-title":"BMJ"},{"key":"5569_CR14","doi-asserted-by":"publisher","first-page":"117437","DOI":"10.1016\/j.ecoenv.2024.117437","volume":"290","author":"X Wu","year":"2025","unstructured":"Wu X, Zhang X, Yu X, et al. Exploring the association between air pollution and the incidence of liver cancers. Ecotoxicol Environ Saf. 2025;290:117437. https:\/\/doi.org\/10.1016\/j.ecoenv.2024.117437.","journal-title":"Ecotoxicol Environ Saf"},{"key":"5569_CR15","doi-asserted-by":"publisher","first-page":"D1257","DOI":"10.1093\/nar\/gkac833","volume":"51","author":"AP Davis","year":"2023","unstructured":"Davis AP, Wiegers TC, Johnson RJ, et al. Comparative toxicogenomics database (CTD): Update 2023. Nucleic Acids Res. 2023;51:D1257\u201362. https:\/\/doi.org\/10.1093\/nar\/gkac833.","journal-title":"Nucleic Acids Res"},{"key":"5569_CR16","doi-asserted-by":"publisher","first-page":"3292","DOI":"10.1038\/s41596-024-01020-z","volume":"19","author":"S Xu","year":"2024","unstructured":"Xu S, Hu E, Cai Y, et al. Using clusterProfiler to characterize multiomics data. Nat Protoc. 2024;19:3292\u2013320. https:\/\/doi.org\/10.1038\/s41596-024-01020-z.","journal-title":"Nat Protoc"},{"key":"5569_CR17","doi-asserted-by":"publisher","first-page":"2498","DOI":"10.1101\/gr.1239303","volume":"13","author":"P Shannon","year":"2003","unstructured":"Shannon P, Markiel A, Ozier O, et al. Cytoscape: A software environment for integrated models of biomolecular interaction networks. Genome Res. 2003;13:2498\u2013504. https:\/\/doi.org\/10.1101\/gr.1239303.","journal-title":"Genome Res"},{"key":"5569_CR18","doi-asserted-by":"publisher","first-page":"118474","DOI":"10.1016\/j.ecoenv.2025.118474","volume":"302","author":"C Cui","year":"2025","unstructured":"Cui C, Yang R, Chen H, et al. Air toxins disorder the NF-kB pathway leads to immune disorders and immune diseases in the human health. Ecotoxicol Environ Saf. 2025;302:118474. https:\/\/doi.org\/10.1016\/j.ecoenv.2025.118474.","journal-title":"Ecotoxicol Environ Saf"},{"key":"5569_CR19","doi-asserted-by":"publisher","first-page":"114266","DOI":"10.1016\/j.ecoenv.2022.114266","volume":"247","author":"X Wang","year":"2022","unstructured":"Wang X, Lu W, Xia X, et al. Selenomethionine mitigate PM2.5-induced cellular senescence in the lung via attenuating inflammatory response mediated by cGAS\/STING\/NF-\u03baB pathway. Ecotoxicol Environ Saf. 2022;247:114266. https:\/\/doi.org\/10.1016\/j.ecoenv.2022.114266.","journal-title":"Ecotoxicol Environ Saf"},{"key":"5569_CR20","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1186\/s43556-024-00184-0","volume":"5","author":"Y Xue","year":"2024","unstructured":"Xue Y, Ruan Y, Wang Y, et al. Signaling pathways in liver cancer: Pathogenesis and targeted therapy. Mol Biomed. 2024;5:20. https:\/\/doi.org\/10.1186\/s43556-024-00184-0.","journal-title":"Mol Biomed"},{"key":"5569_CR21","doi-asserted-by":"publisher","first-page":"101581","DOI":"10.1016\/j.redox.2020.101581","volume":"37","author":"K Ziegler","year":"2020","unstructured":"Ziegler K, Kunert AT, Reinmuth-Selzle K, et al. Chemical modification of pro-inflammatory proteins by peroxynitrite increases activation of TLR4 and NF-\u03baB: implications for the health effects of air pollution and oxidative stress. Redox Biol. 2020;37:101581. https:\/\/doi.org\/10.1016\/j.redox.2020.101581.","journal-title":"Redox Biol"},{"key":"5569_CR22","doi-asserted-by":"publisher","first-page":"e70876","DOI":"10.1096\/fj.202501452R","volume":"39","author":"Y Yuan","year":"2025","unstructured":"Yuan Y, Mu N, Li Y, et al. TNF-\u03b1 promotes synovial inflammation and cartilage bone destruction in rheumatoid arthritis via NF-\u03baB\/YY1\/miR-103a-3p axis. FASEB j: off publ Fed Am Soc Exp Biol. 2025;39:e70876. https:\/\/doi.org\/10.1096\/fj.202501452R.","journal-title":"FASEB j: off publ Fed Am Soc Exp Biol"},{"key":"5569_CR23","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1111\/1365-2656.13647","volume":"91","author":"PA Arancibia","year":"2022","unstructured":"Arancibia PA, Morin PJ. Network topology and patch connectivity affect dynamics in experimental and model metapopulations. J Anim Ecol. 2022;91:496\u2013505. https:\/\/doi.org\/10.1111\/1365-2656.13647.","journal-title":"J Anim Ecol"},{"key":"5569_CR24","doi-asserted-by":"publisher","first-page":"1227","DOI":"10.1136\/ard-2023-224002","volume":"82","author":"K Matsuoka","year":"2023","unstructured":"Matsuoka K, Bakiri L, Bilban M, et al. Metabolic rewiring controlled by c-fos governs cartilage integrity in osteoarthritis. Ann Rheum Dis. 2023;82:1227\u201339. https:\/\/doi.org\/10.1136\/ard-2023-224002.","journal-title":"Ann Rheum Dis"},{"key":"5569_CR25","doi-asserted-by":"publisher","first-page":"e31216","DOI":"10.1002\/jcp.31216","volume":"239","author":"H Yao","year":"2024","unstructured":"Yao H, Wu Y, Zhong Y, et al. Role of c-fos in DNA damage repair. J Cell Physiol. 2024;239:e31216. https:\/\/doi.org\/10.1002\/jcp.31216.","journal-title":"J Cell Physiol"},{"key":"5569_CR26","doi-asserted-by":"publisher","first-page":"102098","DOI":"10.1016\/j.xcrm.2025.102098","volume":"6","author":"Y Liu","year":"2025","unstructured":"Liu Y, Du Z, Li L, et al. scRNA-seq reveals an immune microenvironment and JUN-mediated NK cell exhaustion in relapsed T-ALL. Cell Rep Med. 2025;6:102098. https:\/\/doi.org\/10.1016\/j.xcrm.2025.102098.","journal-title":"Cell Rep Med"},{"key":"5569_CR27","doi-asserted-by":"publisher","first-page":"140946","DOI":"10.1016\/j.jhazmat.2025.140946","volume":"501","author":"L Chen","year":"2026","unstructured":"Chen L, Cui F, Li H, et al. RAD51 m6A and PARylation modification orchestrate benzene-induced haematological toxicity. J Hazard Mater. 2026;501:140946. https:\/\/doi.org\/10.1016\/j.jhazmat.2025.140946.","journal-title":"J Hazard Mater"},{"key":"5569_CR28","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1016\/j.freeradbiomed.2023.12.041","volume":"212","author":"C Hu","year":"2024","unstructured":"Hu C, Ji F, Lv R, et al. Putrescine promotes MMP9-induced angiogenesis in skeletal muscle through hydrogen peroxide\/METTL3 pathway. Free Radic Biol Med. 2024;212:433\u201347. https:\/\/doi.org\/10.1016\/j.freeradbiomed.2023.12.041.","journal-title":"Free Radic Biol Med"},{"key":"5569_CR29","doi-asserted-by":"publisher","first-page":"215834","DOI":"10.1016\/j.canlet.2022.215834","volume":"545","author":"K Chen","year":"2022","unstructured":"Chen K, Wang Y, Hou Y, et al. Single cell RNA-seq reveals the CCL5\/SDC1 receptor-ligand interaction between T cells and tumor cells in pancreatic cancer. Cancer Lett. 2022;545:215834. https:\/\/doi.org\/10.1016\/j.canlet.2022.215834.","journal-title":"Cancer Lett"},{"key":"5569_CR30","doi-asserted-by":"publisher","first-page":"119297","DOI":"10.1016\/j.ecoenv.2025.119297","volume":"306","author":"Y Xu","year":"2025","unstructured":"Xu Y, Wang W, Qiu X-R, et al. Decoding the air pollutant\u2013psoriasis axis: a multi-layered systems toxicology investigation. Ecotoxicol Environ Saf. 2025;306:119297. https:\/\/doi.org\/10.1016\/j.ecoenv.2025.119297.","journal-title":"Ecotoxicol Environ Saf"},{"key":"5569_CR31","doi-asserted-by":"publisher","first-page":"1465","DOI":"10.1158\/1055-9965.EPI-24-0325","volume":"33","author":"D DeMoulin","year":"2024","unstructured":"DeMoulin D, Cai H, Vermeulen R, et al. Occupational benzene exposure and cancer risk among Chinese men: A report from the shanghai men\u2019s health study. Cancer Epidemiol Biomark Prev: Publ Am Assoc Cancer Res Cosponsored Am Soc Prev Oncol. 2024;33:1465\u201374. https:\/\/doi.org\/10.1158\/1055-9965.EPI-24-0325.","journal-title":"Cancer Epidemiol Biomark Prev: Publ Am Assoc Cancer Res Cosponsored Am Soc Prev Oncol"},{"key":"5569_CR32","doi-asserted-by":"publisher","first-page":"e50438","DOI":"10.7759\/cureus.50438","volume":"15","author":"H Fujikawa","year":"2023","unstructured":"Fujikawa H, Ichibayashi R, Sato T, Shimizu M. The experience of using urinary liver-type fatty acid-binding protein for follow-up of toluene poisoning: A case report. Cureus. 2023;15:e50438. https:\/\/doi.org\/10.7759\/cureus.50438.","journal-title":"Cureus"},{"key":"5569_CR33","doi-asserted-by":"publisher","first-page":"104668","DOI":"10.1016\/j.ebiom.2023.104668","volume":"93","author":"R Vilcassim","year":"2023","unstructured":"Vilcassim R, Thurston GD. Gaps and future directions in research on health effects of air pollution. EBioMedicine. 2023;93:104668. https:\/\/doi.org\/10.1016\/j.ebiom.2023.104668.","journal-title":"EBioMedicine"},{"key":"5569_CR34","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1038\/s41573-023-00846-8","volume":"23","author":"YR Miao","year":"2024","unstructured":"Miao YR, Rankin EB, Giaccia AJ. Therapeutic targeting of the functionally elusive TAM receptor family. Nat Rev Drug Discov. 2024;23:201\u201317. https:\/\/doi.org\/10.1038\/s41573-023-00846-8.","journal-title":"Nat Rev Drug Discov"},{"key":"5569_CR35","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1038\/s41419-025-07480-9","volume":"16","author":"I Malikova","year":"2025","unstructured":"Malikova I, Worth A, Aliyeva D, et al. Proteolysis of TAM receptors in autoimmune diseases and cancer: What does it say to us? Cell Death Dis. 2025;16:155. https:\/\/doi.org\/10.1038\/s41419-025-07480-9.","journal-title":"Cell Death Dis"},{"key":"5569_CR36","doi-asserted-by":"publisher","first-page":"1332818","DOI":"10.3389\/fimmu.2024.1332818","volume":"15","author":"D Apostolo","year":"2024","unstructured":"Apostolo D, Ferreira LL, Vincenzi F, et al. From MASH to HCC: The role of Gas6\/TAM receptors. Front Immunol. 2024;15:1332818. https:\/\/doi.org\/10.3389\/fimmu.2024.1332818.","journal-title":"Front Immunol"},{"key":"5569_CR37","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1186\/s12864-022-08498-5","volume":"23","author":"E Sefer","year":"2022","unstructured":"Sefer E. ProbC: joint modeling of epigenome and transcriptome effects in 3D genome. BMC Genomics. 2022;23:287. https:\/\/doi.org\/10.1186\/s12864-022-08498-5.","journal-title":"BMC Genomics"},{"key":"5569_CR38","doi-asserted-by":"publisher","first-page":"D1005","DOI":"10.1093\/nar\/gkaf968","volume":"54","author":"H Wang","year":"2026","unstructured":"Wang H, Mu W, Bao X, et al. CRESTA: A comprehensive transcriptome atlas for cellular response to external stressors. Nucleic Acids Res. 2026;54:D1005\u201316. https:\/\/doi.org\/10.1093\/nar\/gkaf968.","journal-title":"Nucleic Acids Res"},{"key":"5569_CR39","doi-asserted-by":"publisher","first-page":"832","DOI":"10.1016\/j.csbj.2025.02.028","volume":"27","author":"P Monfort-Lanzas","year":"2025","unstructured":"Monfort-Lanzas P, Rungger K, Madersbacher L, Hackl H. Machine learning to dissect perturbations in complex cellular systems. Comput Struct Biotechnol J. 2025;27:832\u201342. https:\/\/doi.org\/10.1016\/j.csbj.2025.02.028.","journal-title":"Comput Struct Biotechnol J"},{"key":"5569_CR40","doi-asserted-by":"publisher","first-page":"2740","DOI":"10.1016\/j.csbj.2024.06.031","volume":"23","author":"R Long","year":"2024","unstructured":"Long R, Suoangbaji null, Ng IO-L, Ho DW-H. LiverSCA: A comprehensive and user-friendly cell atlas in human hepatocellular carcinoma. Comput Struct Biotechnol J. 2024;23:2740\u20135. https:\/\/doi.org\/10.1016\/j.csbj.2024.06.031.","journal-title":"Comput Struct Biotechnol J"},{"key":"5569_CR41","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1186\/s12885-024-12331-5","volume":"24","author":"B Eralp","year":"2024","unstructured":"Eralp B, Sefer E. Reference-free inferring of transcriptomic events in cancer cells on single-cell data. BMC Cancer. 2024;24:607. https:\/\/doi.org\/10.1186\/s12885-024-12331-5.","journal-title":"BMC Cancer"}],"container-title":["Discover Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12672-026-05569-x","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12672-026-05569-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12672-026-05569-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T10:21:46Z","timestamp":1791973306000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12672-026-05569-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,19]]},"references-count":41,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["5569"],"URL":"https:\/\/doi.org\/10.1007\/s12672-026-05569-x","relation":{},"ISSN":["2730-6011"],"issn-type":[{"value":"2730-6011","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,19]]},"assertion":[{"value":"29 March 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 July 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 July 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Not applicable.","order":1,"name":"Ethics","label":"Ethics approval and consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"1444"}}