{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T20:27:21Z","timestamp":1793824041362,"version":"4.6.1"},"reference-count":92,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T00:00:00Z","timestamp":1780876800000},"content-version":"vor","delay-in-days":39,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"the National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82273572"],"award-info":[{"award-number":["82273572"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100002858","name":"the China Postdoctoral Science Foundation","doi-asserted-by":"crossref","award":["2022M710555"],"award-info":[{"award-number":["2022M710555"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Program for Youth Innovation in Future Medicine of Chongqing Medical University","award":["W0172"],"award-info":[{"award-number":["W0172"]}]},{"name":"Public health key specialty construction project of Chongqing"},{"DOI":"10.13039\/501100001809","name":"Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82573031"],"award-info":[{"award-number":["82573031"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Genome Med"],"DOI":"10.1186\/s13073-026-01664-4","type":"journal-article","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T10:46:16Z","timestamp":1777545976000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Integrative multi-omics profiling reveals distinct evolutionary and immunogenic features of brain oligometastasis in lung adenocarcinoma"],"prefix":"10.1186","volume":"18","author":[{"given":"Rongxin","family":"Liao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusheng","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hengqiu","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengmeng","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yihao","family":"Tao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Kong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cancan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunping","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyue","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zaicheng","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongrong","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenzhou","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,30]]},"reference":[{"issue":"suppl4","key":"1664_CR1","doi-asserted-by":"publisher","first-page":"iv1","DOI":"10.1093\/annonc\/mdx222","volume":"28","author":"PE Postmus","year":"2017","unstructured":"Postmus PE, Kerr KM, Oudkerk M, Senan S, Waller DA, Vansteenkiste J, et al. Early and locally advanced non-small-cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals oncology: official J Eur Soc Med Oncol. 2017;28(suppl4):iv1\u201321.","journal-title":"Annals oncology: official J Eur Soc Med Oncol"},{"issue":"1","key":"1664_CR2","doi-asserted-by":"publisher","first-page":"100005","DOI":"10.1016\/j.clnves.2024.100005","volume":"1","author":"S Li","year":"2025","unstructured":"Li S, Shen Y, Dong C, Yin S, Zhou D, Zhou A. The molecular and immune microenvironmental landscape of brain metastases: Implications for novel treatment options. Cell Invest. 2025;1(1):100005.","journal-title":"Cell Invest"},{"issue":"1","key":"1664_CR3","doi-asserted-by":"publisher","first-page":"e173501","DOI":"10.1001\/jamaoncol.2017.3501","volume":"4","author":"P Iyengar","year":"2018","unstructured":"Iyengar P, Wardak Z, Gerber DE, Tumati V, Ahn C, Hughes RS, et al. Consolidative Radiotherapy for Limited Metastatic Non-Small-Cell Lung Cancer: A Phase 2 Randomized Clinical Trial. JAMA Oncol. 2018;4(1):e173501.","journal-title":"JAMA Oncol"},{"issue":"18","key":"1664_CR4","doi-asserted-by":"publisher","first-page":"1558","DOI":"10.1200\/JCO.19.00201","volume":"37","author":"DR Gomez","year":"2019","unstructured":"Gomez DR, Tang C, Zhang J, Blumenschein GR, Hernandez M, Lee JJ, et al. Local Consolidative Therapy Vs. Maintenance Therapy or Observation for Patients With Oligometastatic Non-Small-Cell Lung Cancer: Long-Term Results of a Multi-Institutional, Phase II, Randomized Study. J Clin oncology: official J Am Soc Clin Oncol. 2019;37(18):1558\u201365.","journal-title":"J Clin oncology: official J Am Soc Clin Oncol"},{"issue":"9","key":"1664_CR5","doi-asserted-by":"publisher","first-page":"1283","DOI":"10.1001\/jamaoncol.2019.1449","volume":"5","author":"JM Bauml","year":"2019","unstructured":"Bauml JM, Mick R, Ciunci C, Aggarwal C, Davis C, Evans T, et al. Pembrolizumab After Completion of Locally Ablative Therapy for Oligometastatic Non-Small Cell Lung Cancer: A Phase 2 Trial. JAMA Oncol. 2019;5(9):1283\u201390.","journal-title":"JAMA Oncol"},{"key":"1664_CR6","doi-asserted-by":"crossref","unstructured":"Xiao G, Li L, Tanzhu G, Liu Z, Gao X, Wan X et al. Heterogeneity of tumor immune microenvironment of EGFR\/ALK-positive tumors versus EGFR\/ALK-negative tumors in resected brain metastases from lung adenocarcinoma. J Immunother Cancer. 2023;11(3):e006243.","DOI":"10.1136\/jitc-2022-006243"},{"issue":"1","key":"1664_CR7","doi-asserted-by":"publisher","first-page":"2059874","DOI":"10.1080\/2162402X.2022.2059874","volume":"11","author":"M Li","year":"2022","unstructured":"Li M, Hou X, Sai K, Wu L, Chen J, Zhang B, et al. Immune suppressive microenvironment in brain metastatic non-small cell lung cancer: comprehensive immune microenvironment profiling of brain metastases versus paired primary lung tumors (GASTO 1060). Oncoimmunology. 2022;11(1):2059874.","journal-title":"Oncoimmunology"},{"issue":"14","key":"1664_CR8","first-page":"1754","volume":"25","author":"H Li","year":"2009","unstructured":"Li H, Durbin R. Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinf (Oxford England). 2009;25(14):1754\u201360.","journal-title":"Bioinf (Oxford England)"},{"key":"1664_CR9","doi-asserted-by":"crossref","unstructured":"Li H, Meng L, Wang H, Cui L, Sheng H, Zhao P et al. Precise identification of somatic and germline variants in the absence of matched normal samples. Brief Bioinform. 2024;26(1):bbae677.","DOI":"10.1093\/bib\/bbae677"},{"key":"1664_CR10","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1186\/1471-2105-12-323","volume":"12","author":"B Li","year":"2011","unstructured":"Li B, Dewey CN. RSEM: accurate transcript quantification from RNA-Seq data with or without a reference genome. BMC Bioinformatics. 2011;12:323.","journal-title":"BMC Bioinformatics"},{"issue":"17","key":"1664_CR11","first-page":"i884","volume":"34","author":"S Chen","year":"2018","unstructured":"Chen S, Zhou Y, Chen Y, Gu J. fastp: an ultra-fast all-in-one FASTQ preprocessor. Bioinf (Oxford England). 2018;34(17):i884\u201390.","journal-title":"Bioinf (Oxford England)"},{"issue":"1","key":"1664_CR12","first-page":"15","volume":"29","author":"A Dobin","year":"2013","unstructured":"Dobin A, Davis CA, Schlesinger F, Drenkow J, Zaleski C, Jha S, et al. STAR: ultrafast universal RNA-seq aligner. Bioinf (Oxford England). 2013;29(1):15\u201321.","journal-title":"Bioinf (Oxford England)"},{"issue":"9","key":"1664_CR13","doi-asserted-by":"publisher","first-page":"1650","DOI":"10.1038\/nprot.2016.095","volume":"11","author":"M Pertea","year":"2016","unstructured":"Pertea M, Kim D, Pertea GM, Leek JT, Salzberg SL. Transcript-level expression analysis of RNA-seq experiments with HISAT, StringTie and Ballgown. Nat Protoc. 2016;11(9):1650\u201367.","journal-title":"Nat Protoc"},{"issue":"3","key":"1664_CR14","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1038\/nbt.2514","volume":"31","author":"K Cibulskis","year":"2013","unstructured":"Cibulskis K, Lawrence MS, Carter SL, Sivachenko A, Jaffe D, Sougnez C, et al. Sensitive detection of somatic point mutations in impure and heterogeneous cancer samples. Nat Biotechnol. 2013;31(3):213\u20139.","journal-title":"Nat Biotechnol"},{"issue":"8","key":"1664_CR15","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1101\/gr.9.8.677","volume":"9","author":"ST Sherry","year":"1999","unstructured":"Sherry ST, Ward M, Sirotkin K. dbSNP-database for single nucleotide polymorphisms and other classes of minor genetic variation. Genome Res. 1999;9(8):677\u20139.","journal-title":"Genome Res"},{"issue":"7571","key":"1664_CR16","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1038\/nature15393","volume":"526","author":"A Auton","year":"2015","unstructured":"Auton A, Brooks LD, Durbin RM, Garrison EP, Kang HM, Korbel JO, et al. A global reference for human genetic variation. Nature. 2015;526(7571):68\u201374.","journal-title":"Nature"},{"issue":"7431","key":"1664_CR17","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1038\/nature11690","volume":"493","author":"W Fu","year":"2013","unstructured":"Fu W, O\u2019Connor TD, Jun G, Kang HM, Abecasis G, Leal SM, et al. Analysis of 6,515 exomes reveals the recent origin of most human protein-coding variants. Nature. 2013;493(7431):216\u201320.","journal-title":"Nature"},{"issue":"D1","key":"1664_CR18","doi-asserted-by":"publisher","first-page":"D840","DOI":"10.1093\/nar\/gkw971","volume":"45","author":"KJ Karczewski","year":"2017","unstructured":"Karczewski KJ, Weisburd B, Thomas B, Solomonson M, Ruderfer DM, Kavanagh D, et al. The ExAC browser: displaying reference data information from over 60 000 exomes. Nucleic Acids Res. 2017;45(D1):D840\u20135.","journal-title":"Nucleic Acids Res"},{"issue":"1","key":"1664_CR19","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1038\/nbt.1754","volume":"29","author":"JT Robinson","year":"2011","unstructured":"Robinson JT, Thorvaldsd\u00f3ttir H, Winckler W, Guttman M, Lander ES, Getz G, et al. Integrative genomics viewer. Nat Biotechnol. 2011;29(1):24\u20136.","journal-title":"Nat Biotechnol"},{"issue":"4","key":"1664_CR20","doi-asserted-by":"publisher","first-page":"e1004873","DOI":"10.1371\/journal.pcbi.1004873","volume":"12","author":"E Talevich","year":"2016","unstructured":"Talevich E, Shain AH, Botton T, Bastian BC, CNVkit. Genome-Wide Copy Number Detection and Visualization from Targeted DNA Sequencing. PLoS Comput Biol. 2016;12(4):e1004873.","journal-title":"PLoS Comput Biol"},{"issue":"11","key":"1664_CR21","first-page":"1590","volume":"37","author":"S Wang","year":"2021","unstructured":"Wang S, Tao Z, Wu T, Liu XS. Sigflow: an automated and comprehensive pipeline for cancer genome mutational signature analysis. Bioinf (Oxford England). 2021;37(11):1590\u20132.","journal-title":"Bioinf (Oxford England)"},{"issue":"4","key":"1664_CR22","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1038\/nmeth.2883","volume":"11","author":"A Roth","year":"2014","unstructured":"Roth A, Khattra J, Yap D, Wan A, Laks E, Biele J, et al. PyClone: statistical inference of clonal population structure in cancer. Nat Methods. 2014;11(4):396\u20138.","journal-title":"Nat Methods"},{"issue":"9","key":"1664_CR23","first-page":"1349","volume":"31","author":"S Malikic","year":"2015","unstructured":"Malikic S, McPherson AW, Donmez N, Sahinalp CS. Clonality inference in multiple tumor samples using phylogeny. Bioinf (Oxford England). 2015;31(9):1349\u201356.","journal-title":"Bioinf (Oxford England)"},{"issue":"7382","key":"1664_CR24","doi-asserted-by":"publisher","first-page":"506","DOI":"10.1038\/nature10738","volume":"481","author":"L Ding","year":"2012","unstructured":"Ding L, Ley TJ, Larson DE, Miller CA, Koboldt DC, Welch JS, et al. Clonal evolution in relapsed acute myeloid leukaemia revealed by whole-genome sequencing. Nature. 2012;481(7382):506\u201310.","journal-title":"Nature"},{"issue":"4","key":"1664_CR25","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1038\/s41587-019-0041-2","volume":"37","author":"Y Liu","year":"2019","unstructured":"Liu Y, Siejka-Zieli\u0144ska P, Velikova G, Bi Y, Yuan F, Tomkova M, et al. Bisulfite-free direct detection of 5-methylcytosine and 5-hydroxymethylcytosine at base resolution. Nat Biotechnol. 2019;37(4):424\u20139.","journal-title":"Nat Biotechnol"},{"issue":"18","key":"1664_CR26","first-page":"2847","volume":"32","author":"Z Gu","year":"2016","unstructured":"Gu Z, Eils R, Schlesner M. Complex heatmaps reveal patterns and correlations in multidimensional genomic data. Bioinf (Oxford England). 2016;32(18):2847\u20139.","journal-title":"Bioinf (Oxford England)"},{"issue":"12","key":"1664_CR27","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","volume":"15","author":"MI Love","year":"2014","unstructured":"Love MI, Huber W, Anders S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014;15(12):550.","journal-title":"Genome Biol"},{"key":"1664_CR28","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1186\/1471-2105-14-7","volume":"14","author":"S H\u00e4nzelmann","year":"2013","unstructured":"H\u00e4nzelmann S, Castelo R, Guinney J. GSVA: gene set variation analysis for microarray and RNA-seq data. BMC Bioinformatics. 2013;14:7.","journal-title":"BMC Bioinformatics"},{"issue":"1","key":"1664_CR29","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1016\/j.celrep.2016.12.019","volume":"18","author":"P Charoentong","year":"2017","unstructured":"Charoentong P, Finotello F, Angelova M, Mayer C, Efremova M, Rieder D, et al. Pan-cancer Immunogenomic Analyses Reveal Genotype-Immunophenotype Relationships and Predictors of Response to Checkpoint Blockade. Cell Rep. 2017;18(1):248\u201362.","journal-title":"Cell Rep"},{"issue":"12","key":"1664_CR30","first-page":"1572","volume":"26","author":"MD Wilkerson","year":"2010","unstructured":"Wilkerson MD, Hayes DN. ConsensusClusterPlus: a class discovery tool with confidence assessments and item tracking. Bioinf (Oxford England). 2010;26(12):1572\u20133.","journal-title":"Bioinf (Oxford England)"},{"issue":"3","key":"1664_CR31","doi-asserted-by":"publisher","first-page":"e43","DOI":"10.1002\/imt2.43","volume":"1","author":"Z Gu","year":"2022","unstructured":"Gu Z. Complex heatmap visualization. iMeta. 2022;1(3):e43.","journal-title":"iMeta"},{"issue":"2","key":"1664_CR32","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1101\/gr.196394.115","volume":"26","author":"F J\u00fchling","year":"2016","unstructured":"J\u00fchling F, Kretzmer H, Bernhart SH, Otto C, Stadler PF, Hoffmann S. metilene: fast and sensitive calling of differentially methylated regions from bisulfite sequencing data. Genome Res. 2016;26(2):256\u201362.","journal-title":"Genome Res"},{"issue":"4","key":"1664_CR33","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1016\/j.molcel.2010.05.004","volume":"38","author":"S Heinz","year":"2010","unstructured":"Heinz S, Benner C, Spann N, Bertolino E, Lin YC, Laslo P, et al. Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities. Mol Cell. 2010;38(4):576\u201389.","journal-title":"Mol Cell"},{"issue":"1","key":"1664_CR34","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1038\/ng.3458","volume":"48","author":"MA Castro","year":"2016","unstructured":"Castro MA, de Santiago I, Campbell TM, Vaughn C, Hickey TE, Ross E, et al. Regulators of genetic risk of breast cancer identified by integrative network analysis. Nat Genet. 2016;48(1):12\u201321.","journal-title":"Nat Genet"},{"issue":"W1","key":"1664_CR35","doi-asserted-by":"publisher","first-page":"W98","DOI":"10.1093\/nar\/gkx247","volume":"45","author":"Z Tang","year":"2017","unstructured":"Tang Z, Li C, Kang B, Gao G, Li C, Zhang Z. GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res. 2017;45(W1):W98\u2013102.","journal-title":"Nucleic Acids Res"},{"key":"1664_CR36","doi-asserted-by":"publisher","first-page":"4101","DOI":"10.1016\/j.csbj.2021.07.014","volume":"19","author":"B Gy\u0151rffy","year":"2021","unstructured":"Gy\u0151rffy B. Survival analysis across the entire transcriptome identifies biomarkers with the highest prognostic power in breast cancer. Comput Struct Biotechnol J. 2021;19:4101\u20139.","journal-title":"Comput Struct Biotechnol J"},{"issue":"4","key":"1664_CR37","doi-asserted-by":"publisher","first-page":"452","DOI":"10.1038\/s43018-020-0050-6","volume":"1","author":"E Pleasance","year":"2020","unstructured":"Pleasance E, Titmuss E, Williamson L, Kwan H, Culibrk L, Zhao EY, et al. Pan-cancer analysis of advanced patient tumors reveals interactions between therapy and genomic landscapes. Nat cancer. 2020;1(4):452\u201368.","journal-title":"Nat cancer"},{"issue":"2","key":"1664_CR38","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1016\/j.cell.2018.03.035","volume":"173","author":"F Sanchez-Vega","year":"2018","unstructured":"Sanchez-Vega F, Mina M, Armenia J, Chatila WK, Luna A, La KC, et al. Oncogenic Signaling Pathways in The Cancer Genome Atlas. Cell. 2018;173(2):321\u2013e3710.","journal-title":"Cell"},{"issue":"7547","key":"1664_CR39","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1038\/nature14347","volume":"520","author":"G Gundem","year":"2015","unstructured":"Gundem G, Van Loo P, Kremeyer B, Alexandrov LB, Tubio JMC, Papaemmanuil E, et al. The evolutionary history of lethal metastatic prostate cancer. Nature. 2015;520(7547):353\u20137.","journal-title":"Nature"},{"issue":"9","key":"1664_CR40","doi-asserted-by":"publisher","first-page":"2135","DOI":"10.1093\/annonc\/mdx278","volume":"28","author":"Q Wei","year":"2017","unstructured":"Wei Q, Ye Z, Zhong X, Li L, Wang C, Myers RE, et al. Multiregion whole-exome sequencing of matched primary and metastatic tumors revealed genomic heterogeneity and suggested polyclonal seeding in colorectal cancer metastasis. Annals oncology: official J Eur Soc Med Oncol. 2017;28(9):2135\u201341.","journal-title":"Annals oncology: official J Eur Soc Med Oncol"},{"issue":"5","key":"1664_CR41","doi-asserted-by":"publisher","first-page":"1110","DOI":"10.1016\/j.cell.2014.07.013","volume":"158","author":"N Aceto","year":"2014","unstructured":"Aceto N, Bardia A, Miyamoto DT, Donaldson MC, Wittner BS, Spencer JA, et al. Circulating tumor cell clusters are oligoclonal precursors of breast cancer metastasis. Cell. 2014;158(5):1110\u201322.","journal-title":"Cell"},{"issue":"4","key":"1664_CR42","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1038\/nrc2627","volume":"9","author":"CA Klein","year":"2009","unstructured":"Klein CA. Parallel progression of primary tumours and metastases. Nat Rev Cancer. 2009;9(4):302\u201312.","journal-title":"Nat Rev Cancer"},{"issue":"7","key":"1664_CR43","doi-asserted-by":"publisher","first-page":"1113","DOI":"10.1038\/s41588-019-0423-x","volume":"51","author":"Z Hu","year":"2019","unstructured":"Hu Z, Ding J, Ma Z, Sun R, Seoane JA, Scott Shaffer J, et al. Quantitative evidence for early metastatic seeding in colorectal cancer. Nat Genet. 2019;51(7):1113\u201322.","journal-title":"Nat Genet"},{"issue":"7","key":"1664_CR44","doi-asserted-by":"publisher","first-page":"701","DOI":"10.1038\/s41588-020-0628-z","volume":"52","author":"Z Hu","year":"2020","unstructured":"Hu Z, Li Z, Ma Z, Curtis C. Multi-cancer analysis of clonality and the timing of systemic spread in paired primary tumors and metastases. Nat Genet. 2020;52(7):701\u20138.","journal-title":"Nat Genet"},{"issue":"6282","key":"1664_CR45","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1126\/science.aaf2784","volume":"352","author":"S Turajlic","year":"2016","unstructured":"Turajlic S, Swanton C. Metastasis as an evolutionary process. Sci (New York NY). 2016;352(6282):169\u201375.","journal-title":"Sci (New York NY)"},{"issue":"7463","key":"1664_CR46","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1038\/nature12477","volume":"500","author":"LB Alexandrov","year":"2013","unstructured":"Alexandrov LB, Nik-Zainal S, Wedge DC, Aparicio SA, Behjati S, Biankin AV, et al. Signatures of mutational processes in human cancer. Nature. 2013;500(7463):415\u201321.","journal-title":"Nature"},{"issue":"22","key":"1664_CR47","doi-asserted-by":"publisher","first-page":"2109","DOI":"10.1056\/NEJMoa1616288","volume":"376","author":"M Jamal-Hanjani","year":"2017","unstructured":"Jamal-Hanjani M, Wilson GA, McGranahan N, Birkbak NJ, Watkins TBK, Veeriah S, et al. Tracking the Evolution of Non-Small-Cell Lung Cancer. N Engl J Med. 2017;376(22):2109\u201321.","journal-title":"N Engl J Med"},{"issue":"9","key":"1664_CR48","doi-asserted-by":"publisher","first-page":"2261","DOI":"10.1158\/1078-0432.CCR-15-2834","volume":"22","author":"CY Ock","year":"2016","unstructured":"Ock CY, Keam B, Kim S, Lee JS, Kim M, Kim TM, et al. Pan-Cancer Immunogenomic Perspective on the Tumor Microenvironment Based on PD-L1 and CD8 T-Cell Infiltration. Clin cancer research: official J Am Association Cancer Res. 2016;22(9):2261\u201370.","journal-title":"Clin cancer research: official J Am Association Cancer Res"},{"issue":"11","key":"1664_CR49","doi-asserted-by":"publisher","first-page":"2139","DOI":"10.1158\/0008-5472.CAN-15-0255","volume":"75","author":"MW Teng","year":"2015","unstructured":"Teng MW, Ngiow SF, Ribas A, Smyth MJ. Classifying Cancers Based on T-cell Infiltration and PD-L1. Cancer Res. 2015;75(11):2139\u201345.","journal-title":"Cancer Res"},{"key":"1664_CR50","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1111\/j.1600-065X.2010.00923.x","volume":"236","author":"LM Francisco","year":"2010","unstructured":"Francisco LM, Sage PT, Sharpe AH. The PD-1 pathway in tolerance and autoimmunity. Immunol Rev. 2010;236:219\u201342.","journal-title":"Immunol Rev"},{"issue":"12","key":"1664_CR51","doi-asserted-by":"publisher","first-page":"1355","DOI":"10.1158\/2159-8290.CD-13-0310","volume":"3","author":"EA Akbay","year":"2013","unstructured":"Akbay EA, Koyama S, Carretero J, Altabef A, Tchaicha JH, Christensen CL, et al. Activation of the PD-1 pathway contributes to immune escape in EGFR-driven lung tumors. Cancer Discov. 2013;3(12):1355\u201363.","journal-title":"Cancer Discov"},{"issue":"3","key":"1664_CR52","doi-asserted-by":"publisher","first-page":"e1108514","DOI":"10.1080\/2162402X.2015.1108514","volume":"5","author":"J Koh","year":"2016","unstructured":"Koh J, Jang JY, Keam B, Kim S, Kim MY, Go H, et al. EML4-ALK enhances programmed cell death-ligand 1 expression in pulmonary adenocarcinoma via hypoxia-inducible factor (HIF)-1\u03b1 and STAT3. Oncoimmunology. 2016;5(3):e1108514.","journal-title":"Oncoimmunology"},{"issue":"7","key":"1664_CR53","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1038\/s41568-019-0149-1","volume":"19","author":"JP Friedmann Angeli","year":"2019","unstructured":"Friedmann Angeli JP, Krysko DV, Conrad M. Ferroptosis at the crossroads of cancer-acquired drug resistance and immune evasion. Nat Rev Cancer. 2019;19(7):405\u201314.","journal-title":"Nat Rev Cancer"},{"issue":"4","key":"1664_CR54","doi-asserted-by":"publisher","first-page":"100049","DOI":"10.1016\/j.clnves.2025.100049","volume":"1","author":"Z Dai","year":"2025","unstructured":"Dai Z, Liu J, Zeng L, Shi K, Peng X, Jin Z, et al. Targeting ferroptosis in cancer therapy: Mechanisms, strategies, and clinical applications. Cell Invest. 2025;1(4):100049.","journal-title":"Cell Invest"},{"issue":"8","key":"1664_CR55","doi-asserted-by":"publisher","first-page":"2930","DOI":"10.1172\/JCI91190","volume":"127","author":"M Ayers","year":"2017","unstructured":"Ayers M, Lunceford J, Nebozhyn M, Murphy E, Loboda A, Kaufman DR, et al. IFN-\u03b3-related mRNA profile predicts clinical response to PD-1 blockade. J Clin Investig. 2017;127(8):2930\u201340.","journal-title":"J Clin Investig"},{"issue":"1\u20132","key":"1664_CR56","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1016\/j.cell.2014.12.033","volume":"160","author":"MS Rooney","year":"2015","unstructured":"Rooney MS, Shukla SA, Wu CJ, Getz G, Hacohen N. Molecular and genetic properties of tumors associated with local immune cytolytic activity. Cell. 2015;160(1\u20132):48\u201361.","journal-title":"Cell"},{"issue":"1","key":"1664_CR57","first-page":"128","volume":"4","author":"S Garcia-Recio","year":"2023","unstructured":"Garcia-Recio S, Hinoue T, Wheeler GL, Kelly BJ, Garrido-Castro AC, Pascual T, et al. Multiomics in primary and metastatic breast tumors from the AURORA US network finds microenvironment and epigenetic drivers of metastasis. Nat cancer. 2023;4(1):128\u201347.","journal-title":"Nat cancer"},{"issue":"8","key":"1664_CR58","doi-asserted-by":"publisher","first-page":"1203","DOI":"10.1158\/0008-5472.CAN-22-2236","volume":"83","author":"J Gallon","year":"2023","unstructured":"Gallon J, Rodriguez-Calero A, Benjak A, Akhoundova D, Maletti S, Amstutz U, et al. DNA Methylation Landscapes of Prostate Cancer Brain Metastasis Are Shaped by Early Driver Genetic Alterations. Cancer Res. 2023;83(8):1203\u201313.","journal-title":"Cancer Res"},{"issue":"6","key":"1664_CR59","doi-asserted-by":"publisher","first-page":"692","DOI":"10.4161\/epi.6.6.16196","volume":"6","author":"J Sandoval","year":"2011","unstructured":"Sandoval J, Heyn H, Moran S, Serra-Musach J, Pujana MA, Bibikova M, et al. Validation of a DNA methylation microarray for 450,000 CpG sites in the human genome. Epigenetics. 2011;6(6):692\u2013702.","journal-title":"Epigenetics"},{"issue":"1","key":"1664_CR60","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1016\/j.lungcan.2015.01.020","volume":"88","author":"D Rangachari","year":"2015","unstructured":"Rangachari D, Yamaguchi N, VanderLaan PA, Folch E, Mahadevan A, Floyd SR, et al. Brain metastases in patients with EGFR-mutated or ALK-rearranged non-small-cell lung cancers. Lung cancer (Amsterdam Netherlands). 2015;88(1):108\u201311.","journal-title":"Lung cancer (Amsterdam Netherlands)"},{"issue":"7378","key":"1664_CR61","doi-asserted-by":"publisher","first-page":"490","DOI":"10.1038\/nature10716","volume":"480","author":"MB Stadler","year":"2011","unstructured":"Stadler MB, Murr R, Burger L, Ivanek R, Lienert F, Sch\u00f6ler A, et al. DNA-binding factors shape the mouse methylome at distal regulatory regions. Nature. 2011;480(7378):490\u20135.","journal-title":"Nature"},{"key":"1664_CR62","doi-asserted-by":"crossref","unstructured":"Bian F, Goda C, Wang G, Lan YW, Deng Z, Gao W et al. FOXF1 promotes tumor vessel normalization and prevents lung cancer progression through FZD4. EMBO molecular medicine. 2024;16(5):1063-1090.","DOI":"10.1038\/s44321-024-00064-8"},{"key":"1664_CR63","doi-asserted-by":"crossref","unstructured":"Guan X, Liang J, Xiang Y, Li T, Zhong X. BARX1 repressed FOXF1 expression and activated Wnt\/\u03b2-catenin signaling pathway to drive lung adenocarcinoma. Int J Biol Macromol. 2024;261(Pt 2):129717.","DOI":"10.1016\/j.ijbiomac.2024.129717"},{"issue":"6","key":"1664_CR64","doi-asserted-by":"publisher","first-page":"725","DOI":"10.1016\/j.ccr.2013.04.009","volume":"23","author":"WK Cheung","year":"2013","unstructured":"Cheung WK, Zhao M, Liu Z, Stevens LE, Cao PD, Fang JE, et al. Control of alveolar differentiation by the lineage transcription factors GATA6 and HOPX inhibits lung adenocarcinoma metastasis. Cancer Cell. 2013;23(6):725\u201338.","journal-title":"Cancer Cell"},{"issue":"4","key":"1664_CR65","doi-asserted-by":"publisher","first-page":"377","DOI":"10.2174\/092986707779941032","volume":"14","author":"H Kobayashi","year":"2007","unstructured":"Kobayashi H, Boelte KC, Lin PC. Endothelial cell adhesion molecules and cancer progression. Curr Med Chem. 2007;14(4):377\u201386.","journal-title":"Curr Med Chem"},{"issue":"10","key":"1664_CR66","doi-asserted-by":"publisher","first-page":"2698","DOI":"10.1002\/cncr.10541","volume":"94","author":"LJ Schouten","year":"2002","unstructured":"Schouten LJ, Rutten J, Huveneers HA, Twijnstra A. Incidence of brain metastases in a cohort of patients with carcinoma of the breast, colon, kidney, and lung and melanoma. Cancer. 2002;94(10):2698\u2013705.","journal-title":"Cancer"},{"issue":"1","key":"1664_CR67","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1038\/s41419-021-03410-7","volume":"12","author":"Z Song","year":"2021","unstructured":"Song Z, Yang L, Zhou Z, Li P, Wang W, Cheng G, et al. Genomic profiles and tumor immune microenvironment of primary lung carcinoma and brain oligo-metastasis. Cell Death Dis. 2021;12(1):106.","journal-title":"Cell Death Dis"},{"issue":"20","key":"1664_CR68","doi-asserted-by":"publisher","first-page":"3535","DOI":"10.1002\/cncr.32372","volume":"125","author":"H Wang","year":"2019","unstructured":"Wang H, Ou Q, Li D, Qin T, Bao H, Hou X, et al. Genes associated with increased brain metastasis risk in non-small cell lung cancer: Comprehensive genomic profiling of 61 resected brain metastases versus primary non-small cell lung cancer (Guangdong Association Study of Thoracic Oncology 1036). Cancer. 2019;125(20):3535\u201344.","journal-title":"Cancer"},{"issue":"11","key":"1664_CR69","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1038\/s41568-019-0185-x","volume":"19","author":"JG Reiter","year":"2019","unstructured":"Reiter JG, Baretti M, Gerold JM, Makohon-Moore AP, Daud A, Iacobuzio-Donahue CA, et al. An analysis of genetic heterogeneity in untreated cancers. Nat Rev Cancer. 2019;19(11):639\u201350.","journal-title":"Nat Rev Cancer"},{"issue":"5","key":"1664_CR70","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1038\/nrclinonc.2014.238","volume":"12","author":"K Naxerova","year":"2015","unstructured":"Naxerova K, Jain RK. Using tumour phylogenetics to identify the roots of metastasis in humans. Nat reviews Clin Oncol. 2015;12(5):258\u201372.","journal-title":"Nat reviews Clin Oncol"},{"issue":"11","key":"1664_CR71","doi-asserted-by":"publisher","first-page":"1164","DOI":"10.1158\/2159-8290.CD-15-0369","volume":"5","author":"PK Brastianos","year":"2015","unstructured":"Brastianos PK, Carter SL, Santagata S, Cahill DP, Taylor-Weiner A, Jones RT, et al. Genomic Characterization of Brain Metastases Reveals Branched Evolution and Potential Therapeutic Targets. Cancer Discov. 2015;5(11):1164\u201377.","journal-title":"Cancer Discov"},{"key":"1664_CR72","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.semcancer.2019.09.003","volume":"63","author":"TM Parker","year":"2020","unstructured":"Parker TM, Henriques V, Beltran A, Nakshatri H, Gogna R. Cell competition and tumor heterogeneity. Sem Cancer Biol. 2020;63:1\u201310.","journal-title":"Sem Cancer Biol"},{"issue":"19","key":"1664_CR73","doi-asserted-by":"publisher","first-page":"4875","DOI":"10.1158\/0008-5472.CAN-12-2217","volume":"72","author":"C Swanton","year":"2012","unstructured":"Swanton C. Intratumor heterogeneity: evolution through space and time. Cancer Res. 2012;72(19):4875\u201382.","journal-title":"Cancer Res"},{"issue":"3","key":"1664_CR74","doi-asserted-by":"publisher","first-page":"563","DOI":"10.1016\/j.cell.2022.01.003","volume":"185","author":"B Nguyen","year":"2022","unstructured":"Nguyen B, Fong C, Luthra A, Smith SA, DiNatale RG, Nandakumar S, et al. Genomic characterization of metastatic patterns from prospective clinical sequencing of 25,000 patients. Cell. 2022;185(3):563\u2013e7511.","journal-title":"Cell"},{"issue":"1","key":"1664_CR75","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1186\/s40425-017-0283-9","volume":"5","author":"LME Janssen","year":"2017","unstructured":"Janssen LME, Ramsay EE, Logsdon CD, Overwijk WW. The immune system in cancer metastasis: friend or foe? J Immunother Cancer. 2017;5(1):79.","journal-title":"J Immunother Cancer"},{"issue":"5","key":"1664_CR76","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1038\/ni1582","volume":"9","author":"E Vivier","year":"2008","unstructured":"Vivier E, Tomasello E, Baratin M, Walzer T, Ugolini S. Functions of natural killer cells. Nat Immunol. 2008;9(5):503\u201310.","journal-title":"Nat Immunol"},{"issue":"2","key":"1664_CR77","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1016\/j.ccell.2017.06.009","volume":"32","author":"A L\u00f3pez-Soto","year":"2017","unstructured":"L\u00f3pez-Soto A, Gonzalez S, Smyth MJ, Galluzzi L. Control of Metastasis by NK Cells. Cancer Cell. 2017;32(2):135\u201354.","journal-title":"Cancer Cell"},{"issue":"7864","key":"1664_CR78","doi-asserted-by":"publisher","first-page":"566","DOI":"10.1038\/s41586-021-03614-z","volume":"594","author":"AL Correia","year":"2021","unstructured":"Correia AL, Guimaraes JC, Auf der Maur P, De Silva D, Trefny MP, Okamoto R, et al. Hepatic stellate cells suppress NK cell-sustained breast cancer dormancy. Nature. 2021;594(7864):566\u201371.","journal-title":"Nature"},{"key":"1664_CR79","doi-asserted-by":"publisher","first-page":"1098445","DOI":"10.3389\/fimmu.2022.1098445","volume":"13","author":"M Vyas","year":"2022","unstructured":"Vyas M, Requesens M, Nguyen TH, Peigney D, Azin M, Demehri S. Natural killer cells suppress cancer metastasis by eliminating circulating cancer cells. Front Immunol. 2022;13:1098445.","journal-title":"Front Immunol"},{"key":"1664_CR80","doi-asserted-by":"crossref","unstructured":"Zhang Q, An ZY, Jiang W, Jin WL, He XY. Collagen code in tumor microenvironment: Functions, molecular mechanisms, and therapeutic implications. Volume 166. Biomedecine pharmacother. 2023;166:115390.","DOI":"10.1016\/j.biopha.2023.115390"},{"issue":"4","key":"1664_CR81","doi-asserted-by":"publisher","first-page":"548","DOI":"10.1016\/j.ccell.2021.02.007","volume":"39","author":"Y Chen","year":"2021","unstructured":"Chen Y, Kim J, Yang S, Wang H, Wu CJ, Sugimoto H, et al. Type I collagen deletion in \u03b1SMA+ myofibroblasts augments immune suppression and accelerates progression of pancreatic cancer. Cancer Cell. 2021;39(4):548\u2013. \u2013\u200965.e6.","journal-title":"Cancer Cell"},{"issue":"1","key":"1664_CR82","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1038\/s43018-021-00291-9","volume":"3","author":"JS Di Martino","year":"2022","unstructured":"Di Martino JS, Nobre AR, Mondal C, Taha I, Farias EF, Fertig EJ, et al. A tumor-derived type III collagen-rich ECM niche regulates tumor cell dormancy. Nat cancer. 2022;3(1):90\u2013107.","journal-title":"Nat cancer"},{"issue":"3","key":"1664_CR83","doi-asserted-by":"publisher","first-page":"468","DOI":"10.1016\/j.neuron.2011.03.020","volume":"70","author":"YB Choi","year":"2011","unstructured":"Choi YB, Li HL, Kassabov SR, Jin I, Puthanveettil SV, Karl KA, et al. Neurexin-neuroligin transsynaptic interaction mediates learning-related synaptic remodeling and long-term facilitation in aplysia. Neuron. 2011;70(3):468\u201381.","journal-title":"Neuron"},{"issue":"7215","key":"1664_CR84","doi-asserted-by":"publisher","first-page":"903","DOI":"10.1038\/nature07456","volume":"455","author":"TC S\u00fcdhof","year":"2008","unstructured":"S\u00fcdhof TC. Neuroligins and neurexins link synaptic function to cognitive disease. Nature. 2008;455(7215):903\u201311.","journal-title":"Nature"},{"issue":"6","key":"1664_CR85","doi-asserted-by":"publisher","first-page":"106868","DOI":"10.1016\/j.isci.2023.106868","volume":"26","author":"F Arias-Arag\u00f3n","year":"2023","unstructured":"Arias-Arag\u00f3n F, Trist\u00e1n-Clavijo E, Mart\u00ednez-Gallego I, Robles-Lanuza E, Coatl-Cuaya H, Mart\u00edn-Cuevas C, et al. A Neuroligin-1 mutation associated with Alzheimer\u2019s disease produces memory and age-dependent impairments in hippocampal plasticity. iScience. 2023;26(6):106868.","journal-title":"iScience"},{"key":"1664_CR86","doi-asserted-by":"crossref","unstructured":"Bizzozero L, Pergolizzi M, Pascal D, Maldi E, Villari G, Erriquez J et al. Tumoral Neuroligin 1 Promotes Cancer-Nerve Interactions and Synergizes with the Glial Cell Line-Derived Neurotrophic Factor. Cells. 2022;11(2):280.","DOI":"10.3390\/cells11020280"},{"issue":"1","key":"1664_CR87","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1186\/s13046-022-02465-4","volume":"41","author":"M Pergolizzi","year":"2022","unstructured":"Pergolizzi M, Bizzozero L, Maione F, Maldi E, Isella C, Macagno M, et al. The neuronal protein Neuroligin 1 promotes colorectal cancer progression by modulating the APC\/\u03b2-catenin pathway. J experimental Clin cancer research: CR. 2022;41(1):266.","journal-title":"J experimental Clin cancer research: CR"},{"issue":"Suppl","key":"1664_CR88","doi-asserted-by":"publisher","first-page":"S185","DOI":"10.1016\/j.semcancer.2015.03.004","volume":"35","author":"DS Vinay","year":"2015","unstructured":"Vinay DS, Ryan EP, Pawelec G, Talib WH, Stagg J, Elkord E, et al. Immune evasion in cancer: Mechanistic basis and therapeutic strategies. Sem Cancer Biol. 2015;35(Suppl):S185\u201398.","journal-title":"Sem Cancer Biol"},{"key":"1664_CR89","doi-asserted-by":"crossref","unstructured":"Cornel AM, Mimpen IL, Nierkens S. MHC Class I Downregulation in Cancer: Underlying Mechanisms and Potential Targets for Cancer Immunotherapy. Cancers. 2020;12(7):1760.","DOI":"10.3390\/cancers12071760"},{"issue":"10","key":"1664_CR90","doi-asserted-by":"publisher","first-page":"1953","DOI":"10.1093\/annonc\/mdw289","volume":"27","author":"AS Mansfield","year":"2016","unstructured":"Mansfield AS, Aubry MC, Moser JC, Harrington SM, Dronca RS, Park SS, et al. Temporal and spatial discordance of programmed cell death-ligand 1 expression and lymphocyte tumor infiltration between paired primary lesions and brain metastases in lung cancer. Annals oncology: official J Eur Soc Med Oncol. 2016;27(10):1953\u20138.","journal-title":"Annals oncology: official J Eur Soc Med Oncol"},{"key":"1664_CR91","unstructured":"Rongxin Liao Q, Yu Y, Huang H, He M, Song X, Gao L, Shen Y, Tao L, Li G, Kong XR, Wang C, Huang S, Zhang X, Xu Z, Zhou R. Zhenzhou Yang, Yuan Peng. Integrative Multi-Omics Profiling Reveals Distinct Evolutionary and Immunogenic Features of Brain Oligometastasis in Lung Adenocarcinoma. HRA018046, Genome Sequence Archive. https:\/\/ngdc.cncb.ac.cn\/gsa-human\/s\/nL56B21E."},{"key":"1664_CR92","unstructured":"Rongxin Liao Q, Yu Y, Huang H, He M, Song X, Gao L, Shen Y, Tao L, Li G, Kong XR, Wang C, Huang S, Zhang X, Xu Z. Rongrong Zhou, Zhenzhou Yang, Yuan Peng. Integrative Multi-Omics Profiling Reveals Distinct Evolutionary and Immunogenic Features of Brain Oligometastasis in Lung Adenocarcinoma. Github. https:\/\/github.com\/smengmeng30-dev\/luad-oligo-bm-multiomics\/."}],"container-title":["Genome Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13073-026-01664-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13073-026-01664-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13073-026-01664-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T15:02:41Z","timestamp":1780930961000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s13073-026-01664-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,30]]},"references-count":92,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["1664"],"URL":"https:\/\/doi.org\/10.1186\/s13073-026-01664-4","relation":{},"ISSN":["1756-994X"],"issn-type":[{"value":"1756-994X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,30]]},"assertion":[{"value":"16 April 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 April 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 April 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study involving human tissue samples was approved by the Ethics Committee of Chongqing Medical University (Reference No. 2020\u2009\u2212\u2009171). Written informed consent was obtained from each participant prior to enrollment. All procedures were conducted in accordance with the principles of the Helsinki Declaration and under the supervision of the ethics committee. All animal experiments were approved by the Animal Ethics Committee of the Second Affiliated Hospital of Chongqing Medical University (Reference No. 2022\u2009\u2212\u2009285) and were performed in accordance with the relevant institutional guidelines and regulations for animal care and use.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"82"}}