{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T18:05:30Z","timestamp":1780596330541,"version":"3.54.1"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T00:00:00Z","timestamp":1780531200000},"content-version":"vor","delay-in-days":34,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fundamental Research Funds","award":["2572023AW42"],"award-info":[{"award-number":["2572023AW42"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32470687"],"award-info":[{"award-number":["32470687"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["62502083"],"award-info":[{"award-number":["62502083"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["62225109"],"award-info":[{"award-number":["62225109"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,5,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Long noncoding RNAs (lncRNAs) play critical roles in regulating stemness signature genes (SSGs) and tumor immunity, thereby shaping the tumor microenvironment and antitumor immune responses. Increasing evidence suggests that cancer stem cell traits are closely associated with immune evasion and therapeutic resistance, underscoring the need to systematically characterize the pan-cancer interplay among SSGs, lncRNAs, and tumor immunity. Here, we developed an integrative analytical framework that combines network-based modeling with Bayesian network inference to identify core regulatory triplets (STEM-LncCRTs), each consisting of an lncRNA, an SSG, and an immune gene. We demonstrate that specific stemness-related lncRNAs can distinguish cancer subtypes, and that common stemness-related lncRNAs correlate significantly with immune cell infiltration. Notably, the ATAD5\/PRR11-AS1\/SKP2 triplet exhibits favorable prognostic potential across multiple cancers and consistently outperforms individual gene markers in predicting 1-, 3-, and 5-year overall survival. Furthermore, using four machine learning algorithms across three independent immunotherapy cohorts, we validate the predictive value of STEM-LncCRTs for immune checkpoint inhibitor response. Importantly, integrating STEM-LncCRTs with tumor mutation burden further improves predictive accuracy. Collectively, this study provides a systems-level view of stemness-related lncRNA regulation in tumor immunity and offers practical biomarkers for predicting immunotherapy efficacy.<\/jats:p>","DOI":"10.1093\/bib\/bbag287","type":"journal-article","created":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T11:37:49Z","timestamp":1779190669000},"source":"Crossref","is-referenced-by-count":0,"title":["Identification and characterization of lncRNA-stemness-immune regulatory patterns"],"prefix":"10.1093","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-1476-9707","authenticated-orcid":false,"given":"Zhipeng","family":"Qian","sequence":"first","affiliation":[{"name":"College of Life Sciences, Northeast Forestry University , No. 26 Hexing Road, Xiangfang District, Harbin, Heilongjiang 150040 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaqi","family":"Yin","sequence":"additional","affiliation":[{"name":"College of Computer and Control Engineering, Northeast Forestry University , No. 26 Hexing Road, Xiangfang District, Harbin, Heilongjiang 150040 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8546-9665","authenticated-orcid":false,"given":"Chunlong","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Computer and Control Engineering, Northeast Forestry University , No. 26 Hexing Road, Xiangfang District, Harbin, Heilongjiang 150040 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7381-2374","authenticated-orcid":false,"given":"Guohua","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Computer and Control Engineering, Northeast Forestry University , No. 26 Hexing Road, Xiangfang District, Harbin, Heilongjiang 150040 ,","place":["China"]},{"name":"School of Computer Science and Technology, Harbin Institute of Technology , No. 92 Xidazhi Street, Nangang District, Harbin, Heilongjiang 150001 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2965-9920","authenticated-orcid":false,"given":"Chunyu","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Computer Science and Technology, Harbin Institute of Technology , No. 92 Xidazhi Street, Nangang District, Harbin, Heilongjiang 150001 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0403-7287","authenticated-orcid":false,"given":"Yang","family":"Li","sequence":"additional","affiliation":[{"name":"College of Computer and Control Engineering, Northeast Forestry University , No. 26 Hexing Road, Xiangfang District, Harbin, Heilongjiang 150040 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7219-0999","authenticated-orcid":false,"given":"Yuming","family":"Zhao","sequence":"additional","affiliation":[{"name":"College of Life Sciences, Northeast Forestry University , No. 26 Hexing Road, Xiangfang District, Harbin, Heilongjiang 150040 ,","place":["China"]},{"name":"College of Computer and Control Engineering, Northeast Forestry University , No. 26 Hexing Road, Xiangfang District, Harbin, Heilongjiang 150040 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,6,4]]},"reference":[{"key":"2026060413251879700_ref1","doi-asserted-by":"crossref","first-page":"1811","DOI":"10.1016\/S0140-6736(25)01917-8","article-title":"Global burden of 292 causes of death in 204 countries and territories and 660 subnational locations, 1990-2023: a systematic analysis for the global burden of disease study 2023","volume":"406","author":"Collaborators GBDCoD","year":"2025","journal-title":"Lancet"},{"key":"2026060413251879700_ref2","doi-asserted-by":"publisher","first-page":"448","DOI":"10.21037\/jtd.2017.02.75","article-title":"Cancer prevention from the perspective of global cancer burden patterns","volume":"9","author":"Nagai","year":"2017","journal-title":"J Thorac Dis"},{"key":"2026060413251879700_ref3","doi-asserted-by":"publisher","first-page":"e204564","DOI":"10.1001\/jamaoncol.2020.4564","article-title":"Efficacy and safety of Nivolumab plus Ipilimumab in patients with advanced hepatocellular carcinoma previously treated with Sorafenib the CheckMate 040 randomized clinical trial","volume":"6","author":"Yau","year":"2020","journal-title":"Jama Oncol"},{"key":"2026060413251879700_ref4","doi-asserted-by":"publisher","first-page":"860","DOI":"10.1016\/j.scib.2023.03.050","article-title":"Development and clinical application of human mesenchymal stem cell drugs","volume":"68","author":"Liu","year":"2023","journal-title":"Sci Bull"},{"key":"2026060413251879700_ref5","doi-asserted-by":"publisher","first-page":"9020","DOI":"10.1073\/pnas.1818210116","article-title":"Cancer stemness, intratumoral heterogeneity, and immune response across cancers","volume":"116","author":"Miranda","year":"2019","journal-title":"Proc Natl Acad Sci USA"},{"key":"2026060413251879700_ref6","doi-asserted-by":"publisher","first-page":"780","DOI":"10.1007\/s12094-006-0132-7","article-title":"Gene expression regulation and cancer","volume":"8","author":"Delgado","year":"2006","journal-title":"Clin Transl Oncol"},{"key":"2026060413251879700_ref7","doi-asserted-by":"publisher","first-page":"1237","DOI":"10.1016\/j.cell.2013.02.014","article-title":"Transcriptional regulation and its misregulation in disease","volume":"152","author":"Lee","year":"2013","journal-title":"Cell"},{"key":"2026060413251879700_ref8","doi-asserted-by":"publisher","first-page":"1253","DOI":"10.1038\/nm.3981","article-title":"The emerging role of lncRNAs in cancer","volume":"21","author":"Huarte","year":"2015","journal-title":"Nat Med"},{"key":"2026060413251879700_ref9","doi-asserted-by":"publisher","first-page":"7384","DOI":"10.7150\/thno.37892","article-title":"LncCCAT1 promotes breast cancer stem cell function through activating WNT\/\u03b2-catenin signaling","volume":"9","author":"Tang","year":"2019","journal-title":"Theranostics"},{"key":"2026060413251879700_ref10","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1186\/s12943-021-01469-6","article-title":"LncRNA PKMYT1AR promotes cancer stem cell maintenance in non-small cell lung cancer via activating Wnt signaling pathway","volume":"20","author":"He","year":"2021","journal-title":"Mol Cancer"},{"key":"2026060413251879700_ref11","doi-asserted-by":"publisher","first-page":"7526","DOI":"10.1038\/s41467-023-43113-5","article-title":"LncRNA INHEG promotes glioma stem cell maintenance and tumorigenicity through regulating rRNA 2'-O-methylation","volume":"14","author":"Liu","year":"2023","journal-title":"Nat Commun"},{"key":"2026060413251879700_ref12","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1186\/s12967-021-02936-w","article-title":"TPM, FPKM, or normalized counts? A comparative study of quantification measures for the analysis of RNA-seq data from the NCI patient-derived models repository","volume":"19","author":"Zhao","year":"2021","journal-title":"J Transl Med"},{"key":"2026060413251879700_ref13","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1016\/j.gpb.2022.08.004","article-title":"TIGER: a web portal of tumor immunotherapy gene expression resource","volume":"21","author":"Chen","year":"2023","journal-title":"Genom Proteom Bioinf"},{"key":"2026060413251879700_ref14","doi-asserted-by":"publisher","first-page":"W72","DOI":"10.1093\/nar\/gkv529","article-title":"StemChecker: a web-based tool to discover and explore stemness signatures in gene sets","volume":"43","author":"Pinto","year":"2015","journal-title":"Nucleic Acids Res"},{"key":"2026060413251879700_ref15","doi-asserted-by":"publisher","first-page":"D991","DOI":"10.1093\/nar\/gks1193","article-title":"NCBI GEO: archive for functional genomics data sets-update","volume":"41","author":"Barrett","year":"2013","journal-title":"Nucleic Acids Res"},{"key":"2026060413251879700_ref16","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1038\/nature24277","article-title":"Genetic effects on gene expression across human tissues","volume":"550","author":"Aguet","year":"2017","journal-title":"Nature"},{"key":"2026060413251879700_ref17","doi-asserted-by":"publisher","first-page":"170030","DOI":"10.1038\/sdata.2017.30","article-title":"Molecular, phenotypic, and sample-associated data to describe pluripotent stem cell lines and derivatives","volume":"4","author":"Daily","year":"2017","journal-title":"Sci Data"},{"key":"2026060413251879700_ref18","doi-asserted-by":"publisher","first-page":"D607","DOI":"10.1093\/nar\/gky1131","article-title":"STRING v11: protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets","volume":"47","author":"Szklarczyk","year":"2019","journal-title":"Nucleic Acids Res"},{"key":"2026060413251879700_ref19","doi-asserted-by":"publisher","first-page":"1917","DOI":"10.1126\/science.1151526","article-title":"Induced pluripotent stem cell lines derived from human somatic cells","volume":"318","author":"Yu","year":"2007","journal-title":"Science"},{"key":"2026060413251879700_ref20","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1016\/j.mehy.2018.03.012","article-title":"KLF4 signalling in carcinogenesis and epigenetic regulation of hTERT","volume":"115","author":"Yadav","year":"2018","journal-title":"Med Hypotheses"},{"key":"2026060413251879700_ref21","doi-asserted-by":"publisher","first-page":"eaan2507","DOI":"10.1126\/science.aan2507","article-title":"A pathology atlas of the human cancer transcriptome","volume":"357","author":"Uhlen","year":"2017","journal-title":"Science"},{"key":"2026060413251879700_ref22","doi-asserted-by":"publisher","first-page":"542","DOI":"10.1016\/j.cell.2017.01.010","article-title":"Genomic and transcriptomic features of response to anti-PD-1 therapy in metastatic melanoma","volume":"168","author":"Hugo","year":"2017","journal-title":"Cell"},{"key":"2026060413251879700_ref23","doi-asserted-by":"publisher","first-page":"934","DOI":"10.1016\/j.cell.2017.09.028","article-title":"Tumor and microenvironment evolution during immunotherapy with Nivolumab","volume":"171","author":"Riaz","year":"2017","journal-title":"Cell"},{"key":"2026060413251879700_ref24","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1126\/science.aad0095","article-title":"Genomic correlates of response to CTLA-4 blockade in metastatic melanoma","volume":"350","author":"Van Allen","year":"2015","journal-title":"Science"},{"key":"2026060413251879700_ref25","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1016\/j.cell.2018.03.034","article-title":"Machine learning identifies stemness features associated with oncogenic dedifferentiation","volume":"173","author":"Malta","year":"2018","journal-title":"Cell"},{"key":"2026060413251879700_ref26","doi-asserted-by":"publisher","first-page":"7018","DOI":"10.1038\/s41598-018-25451-3","article-title":"LncRNA OIP5-AS1 is overexpressed in undifferentiated oral tumors and integrated analysis identifies as a downstream effector of stemness-associated transcription factors","volume":"8","author":"Arunkumar","year":"2018","journal-title":"Sci Rep"},{"key":"2026060413251879700_ref27","doi-asserted-by":"publisher","first-page":"1104","DOI":"10.1002\/tox.23468","article-title":"Long noncoding RNA OIP5-AS1 promotes the stemness of lung cancer cells through enhancing Oct4 mRNA stability","volume":"37","author":"Mao","year":"2022","journal-title":"Environ Toxicol"},{"key":"2026060413251879700_ref28","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1038\/s41434-020-0123-2","article-title":"LncRNA OIP5-AS1 interacts with miR-363-3p to contribute to hepatocellular carcinoma progression through up-regulation of SOX4","volume":"27","author":"Wang","year":"2019","journal-title":"Gene Ther"},{"key":"2026060413251879700_ref29","doi-asserted-by":"publisher","first-page":"BSR20193489","DOI":"10.1042\/BSR20193489","article-title":"NORAD accelerates chemo-resistance of non-small-cell lung cancer via targeting at miR-129-1-3p\/SOX4 axis","volume":"40","author":"Huang","year":"2020","journal-title":"Biosci Rep"},{"key":"2026060413251879700_ref30","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1186\/s13287-022-02913-0","article-title":"Characterization of stem cell landscape and identification of stemness-relevant prognostic gene signature to aid immunotherapy in colorectal cancer","volume":"13","author":"Zheng","year":"2022","journal-title":"Stem Cell Res Ther"},{"key":"2026060413251879700_ref31","doi-asserted-by":"publisher","first-page":"154329","DOI":"10.1016\/j.prp.2023.154329","article-title":"MUC1 promotes cancer stemness and predicts poor prognosis in osteosarcoma","volume":"242","author":"Liu","year":"2023","journal-title":"Pathol Res Pract"},{"key":"2026060413251879700_ref32","doi-asserted-by":"publisher","first-page":"360","DOI":"10.7150\/ijbs.66913","article-title":"Integrated machine learning and bioinformatic analyses constructed a novel stemness-related classifier to predict prognosis and immunotherapy responses for hepatocellular carcinoma patients","volume":"18","author":"Chen","year":"2022","journal-title":"Int J Biol Sci"},{"key":"2026060413251879700_ref33","doi-asserted-by":"publisher","first-page":"118665","DOI":"10.1016\/j.lfs.2020.118665","article-title":"NORAD, a critical long non-coding RNA in human cancers","volume":"264","author":"Soghli","year":"2021","journal-title":"Life Sci"},{"key":"2026060413251879700_ref34","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1007\/s12094-022-02904-w","article-title":"The role of LncRNA MCM3AP-AS1 in human cancer","volume":"25","author":"Azizidoost","year":"2023","journal-title":"Clin Transl Oncol"},{"key":"2026060413251879700_ref35","doi-asserted-by":"publisher","first-page":"11026","DOI":"10.1080\/21655979.2022.2067292","article-title":"The role of long non-coding RNA FGD5-AS1 in cancer","volume":"13","author":"He","year":"2022","journal-title":"Bioengineered"},{"key":"2026060413251879700_ref36","doi-asserted-by":"publisher","first-page":"e201911053","DOI":"10.1083\/jcb.201911053","article-title":"Stem cells in cancer initiation and progression","volume":"219","author":"Bajaj","year":"2020","journal-title":"J Cell Biol"},{"key":"2026060413251879700_ref37","doi-asserted-by":"publisher","first-page":"692940","DOI":"10.3389\/fcell.2021.692940","article-title":"Cancer stem cells: emerging key players in immune evasion of cancers","volume":"9","author":"Lei","year":"2021","journal-title":"Front Cell Dev Biol"},{"key":"2026060413251879700_ref38","doi-asserted-by":"publisher","first-page":"1379","DOI":"10.1038\/s41590-022-01290-3","article-title":"Type I IFNs promote cancer cell stemness by triggering the epigenetic regulator KDM1B","volume":"23","author":"Musella","year":"2022","journal-title":"Nat Immunol"},{"key":"2026060413251879700_ref39","doi-asserted-by":"publisher","first-page":"1000","DOI":"10.1038\/s41467-020-14802-2","article-title":"Pan-cancer characterization of immune-related lncRNAs identifies potential oncogenic biomarkers","volume":"11","author":"Li","year":"2020","journal-title":"Nat Commun"}],"container-title":["Briefings in Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bib\/article-pdf\/27\/3\/bbag287\/68476368\/bbag287.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bib\/article-pdf\/27\/3\/bbag287\/68476368\/bbag287.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T17:25:26Z","timestamp":1780593926000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bib\/article\/doi\/10.1093\/bib\/bbag287\/8702544"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5]]},"references-count":39,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,5,4]]}},"URL":"https:\/\/doi.org\/10.1093\/bib\/bbag287","relation":{},"ISSN":["1467-5463","1477-4054"],"issn-type":[{"value":"1467-5463","type":"print"},{"value":"1477-4054","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,5]]},"published":{"date-parts":[[2026,5]]},"article-number":"bbag287"}}