{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T15:04:17Z","timestamp":1784991857211,"version":"3.55.0"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,1,20]],"date-time":"2022-01-20T00:00:00Z","timestamp":1642636800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012659","name":"Foundation for Innovative Research Groups of the National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002767","name":"Hunan Provincial Science and Technology Department","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002767","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> Head and neck squamous cell carcinoma (HNSCC) is one of the most aggressive malignant cancers worldwide, and accurate prognostic models are urgently needed. Emerging evidence revealed that long non-coding RNAs (lncRNAs) are related to genomic instability. We sought to identify and validate a genomic instability-associated lncRNA prognostic signature to assess HNSCC patient survival outcomes.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> RNA-sequencing data, somatic mutation files, and patient clinical data were downloaded from The Cancer Genome Atlas database. A total of 491 patients with completely clinical files were randomly divided into training and testing sets. In the training set, genomic instability-associated lncRNAs were screened through univariate Cox regression analyses and least absolute shrinkage and selection operator regression analyses to build a genomic instability-associated lncRNA signature (GILncSig). In addition, time-dependent receiver operating characteristic (ROC) curve, Kaplan-Meier survival curve, and clinical stratification analyses were used to evaluate the signature\u2019s reliability. Finally, <jats:italic>in situ<\/jats:italic> hybridization experiments were performed to validate GILncSig expression levels between adjacent non-tumor tissues and tumor tissues from HNSCC patients.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> Four genomic instability-associated lncRNAs (AC023310.4, AC091729.1, LINC01564, and MIR3142HG) were selected for the prognostic signature. The model was successfully validated using the testing cohort. ROC analysis demonstrated its strong predictive ability for HNSCC prognosis. Univariate and multivariate Cox analyses revealed that the GILncSig was an independent predictor of prognosis. HNSCC patients with a low-risk score showed a substantially better prognosis than the high-risk groups. The <jats:italic>in situ<\/jats:italic> hybridization experiments using human HNSCC tissue revealed high GILncSig expression in HNSCC tissues compared with adjacent non-tumor tissues.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> We developed a novel GILncSig for prognosis prediction in HNSCC patients, and the components of that signature might be therapeutic targets for HNSCC.<\/jats:p>","DOI":"10.3389\/fcell.2021.787766","type":"journal-article","created":{"date-parts":[[2022,1,20]],"date-time":"2022-01-20T07:27:55Z","timestamp":1642663675000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Identification and Validation of a Novel Genomic Instability-Associated Long Non-Coding RNA Prognostic Signature in Head and Neck Squamous Cell Carcinoma"],"prefix":"10.3389","volume":"9","author":[{"given":"Yun","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaqiong","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruohuang","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,1,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1056\/nejmoa0912217","article-title":"Human Papillomavirus and Survival of Patients with Oropharyngeal Cancer","volume":"363","author":"Ang","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"B2","doi-asserted-by":"publisher","first-page":"2738","DOI":"10.1016\/j.bbagen.2018.08.016","article-title":"Anti-cancer Activities of Bharangin against Breast Cancer: Evidence for the Role of NF-\u039ab and lncRNAs","volume":"1862","author":"Awasthee","year":"2018","journal-title":"Biochim. Biophys. Acta (Bba) - Gen. Subjects"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1742","DOI":"10.1093\/bib\/bbz118","article-title":"Computational Identification of Mutator-Derived lncRNA Signatures of Genome Instability for Improving the Clinical Outcome of Cancers: a Case Study in Breast Cancer","volume":"21","author":"Bao","year":"2020","journal-title":"Brief. Bioinformatics"},{"key":"B4","doi-asserted-by":"publisher","first-page":"4835","DOI":"10.1038\/s41388-019-0761-2","article-title":"MDM2 Promotes Genome Instability by Ubiquitinating the Transcription Factor HBP1","volume":"38","author":"Cao","year":"2019","journal-title":"Oncogene"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1012","DOI":"10.26355\/eurrev_201902_16988","article-title":"lncRNA-RMRP Promotes Proliferation, Migration and Invasion of Bladder Cancer via miR-206","volume":"23","author":"Cao","year":"2019","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"B6","first-page":"6887","article-title":"Non Coding RNAs in Head and Neck Squamous Cell Carcinoma (HNSCC): a Clinical Perspective","volume":"34","author":"Denaro","year":"2014","journal-title":"Anticancer Res."},{"key":"B7","doi-asserted-by":"publisher","first-page":"5811","DOI":"10.1038\/s41388-018-0382-1","article-title":"Hypoxia-induced LncRNA-Bx111 Promotes Metastasis and Progression of Pancreatic Cancer through Regulating ZEB1 Transcription","volume":"37","author":"Deng","year":"2018","journal-title":"Oncogene"},{"key":"B8","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1016\/j.molmed.2019.04.004","article-title":"Mechanisms of Genomic Instability in Breast Cancer","volume":"25","author":"Duijf","year":"2019","journal-title":"Trends Molecular Medicine"},{"key":"B9","doi-asserted-by":"publisher","first-page":"S5","DOI":"10.1016\/j.semcancer.2015.03.005","article-title":"Genomic Instability in Human Cancer: Molecular Insights and Opportunities for Therapeutic Attack and Prevention through Diet and Nutrition","volume":"35","author":"Ferguson","year":"2015","journal-title":"Semin. Cancer Biol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"E359","DOI":"10.1002\/ijc.29210","article-title":"Cancer Incidence and Mortality Worldwide: Sources, Methods and Major Patterns in GLOBOCAN 2012","volume":"136","author":"Ferlay","year":"2015","journal-title":"Int. J. Cancer"},{"key":"B11","doi-asserted-by":"publisher","first-page":"1","DOI":"10.18637\/jss.v033.i01","article-title":"Regularization Paths for Generalized Linear Models via Coordinate Descent","volume":"33","author":"Friedman","year":"2010","journal-title":"J. Stat. Softw."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1139","DOI":"10.1007\/s13311-018-0649-9","article-title":"LncRNA PVT1 Facilitates Tumorigenesis and Progression of Glioma via Regulation of MiR-128-3p\/GREM1 Axis and BMP Signaling Pathway","volume":"15","author":"Fu","year":"2018","journal-title":"Neurotherapeutics"},{"key":"B13","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1097\/coc.0000000000000587","article-title":"Evaluation of Genetic Variants in MIR3142HG in Susceptibility to and Prognosis of Glioma","volume":"43","author":"Guo","year":"2020","journal-title":"Am. J. Clin. Oncol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1552","DOI":"10.1002\/ijc.24017","article-title":"The Gene Expression Signature of Genomic Instability in Breast Cancer Is an Independent Predictor of Clinical Outcome","volume":"124","author":"Habermann","year":"2009","journal-title":"Int. J. Cancer"},{"key":"B15","doi-asserted-by":"publisher","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of Cancer: the Next Generation","volume":"144","author":"Hanahan","year":"2011","journal-title":"Cell"},{"key":"B16","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/s0092-8674(00)81683-9","article-title":"The Hallmarks of Cancer","volume":"100","author":"Hanahan","year":"2000","journal-title":"Cell"},{"key":"B17","doi-asserted-by":"publisher","first-page":"492","DOI":"10.1038\/s41556-018-0066-7","article-title":"GUARDIN Is a P53-Responsive Long Non-coding RNA that Is Essential for Genomic Stability","volume":"20","author":"Hu","year":"2018","journal-title":"Nat. Cel Biol"},{"key":"B18","doi-asserted-by":"publisher","first-page":"8395","DOI":"10.2147\/ott.s257200","article-title":"Identification and Clinical Validation of 4-lncRNA Signature for Predicting Survival in Head and Neck Squamous Cell Carcinoma","volume":"13","author":"Ji","year":"2020","journal-title":"Ott"},{"key":"B19","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1186\/s12943-016-0545-z","article-title":"Long Non-coding RNAs: Potential New Biomarkers for Predicting Tumor Invasion and Metastasis","volume":"15","author":"Jiang","year":"2016","journal-title":"Mol. Cancer"},{"key":"B20","doi-asserted-by":"publisher","first-page":"3396","DOI":"10.1245\/s10434-020-09210-1","article-title":"A Novel Three-lncRNA Signature Predicts the Overall Survival of HNSCC Patients","volume":"28","author":"Jiang","year":"2021","journal-title":"Ann. Surg. Oncol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1038\/s41572-020-00224-3","article-title":"Head and Neck Squamous Cell Carcinoma","volume":"6","author":"Johnson","year":"2020","journal-title":"Nat. Rev. Dis. Primers"},{"key":"B22","doi-asserted-by":"publisher","first-page":"706","DOI":"10.1002\/jcp.29898","article-title":"Identification of Novel Genes in Testicular Cancer Microenvironment Based on ESTIMATE Algorithm-Derived Immune Scores","volume":"236","author":"Ke","year":"2021","journal-title":"J. Cel Physiol"},{"key":"B23","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/j.cell.2015.12.017","article-title":"Noncoding RNA NORAD Regulates Genomic Stability by Sequestering PUMILIO Proteins","volume":"164","author":"Lee","year":"2016","journal-title":"Cell"},{"key":"B24","doi-asserted-by":"publisher","first-page":"1149","DOI":"10.1038\/cr.2016.111","article-title":"Identification of TRA2B-DNAH5 Fusion as a Novel Oncogenic Driver in Human Lung Squamous Cell Carcinoma","volume":"26","author":"Li","year":"2016","journal-title":"Cell Res"},{"key":"B25","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1038\/nature10760","article-title":"The DNA Damage Response and Cancer Therapy","volume":"481","author":"Lord","year":"2012","journal-title":"Nature"},{"key":"B26","doi-asserted-by":"publisher","first-page":"3930","DOI":"10.7150\/jca.52286","article-title":"Heterogeneity Analysis of Esophageal Squamous Cell Carcinoma in Cell Lines, Tumor Tissues and Patient-Derived Xenografts","volume":"12","author":"Ma","year":"2021","journal-title":"J. Cancer"},{"key":"B27","doi-asserted-by":"publisher","first-page":"1457","DOI":"10.3389\/fonc.2020.01457","article-title":"Mutational Landscape of Esophageal Squamous Cell Carcinoma in an Indian Cohort","volume":"10","author":"Mangalaparthi","year":"2020","journal-title":"Front. Oncol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"386","DOI":"10.1016\/j.mayocp.2015.12.017","article-title":"Head and Neck Squamous Cell Carcinoma: Update on Epidemiology, Diagnosis, and Treatment","volume":"91","author":"Marur","year":"2016","journal-title":"Mayo Clinic Proc."},{"key":"B29","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1146\/annurev-genet-112414-055205","article-title":"Modulation of Chromatin by Noncoding RNA","volume":"49","author":"Meller","year":"2015","journal-title":"Annu. Rev. Genet."},{"key":"B30","doi-asserted-by":"publisher","first-page":"219","DOI":"10.5301\/jbm.2010.6079","article-title":"A 12-gene Genomic Instability Signature Predicts Clinical Outcomes in Multiple Cancer Types","volume":"25","author":"Mettu","year":"2010","journal-title":"Int. J. Biol. Markers"},{"key":"B31","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1038\/s41586-018-0453-z","article-title":"The NORAD lncRNA Assembles a Topoisomerase Complex Critical for Genome Stability","volume":"561","author":"Munschauer","year":"2018","journal-title":"Nature"},{"key":"B32","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1016\/j.oraloncology.2016.05.014","article-title":"Unraveling the Oral Cancer lncRNAome: Identification of Novel lncRNAs Associated with Malignant Progression and HPV Infection","volume":"59","author":"Nohata","year":"2016","journal-title":"Oral Oncol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"vii97","DOI":"10.1093\/annonc\/mdl960","article-title":"Patterns of Genomic Instability in Gastric Cancer: Clinical Implications and Perspectives","volume":"17","author":"Ottini","year":"2006","journal-title":"Ann. Oncol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1186\/s13046-019-1096-0","article-title":"Landscape of Tumor Suppressor Long Noncoding RNAs in Breast Cancer","volume":"38","author":"Pang","year":"2019","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"B35","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1007\/s10555-013-9429-5","article-title":"The Detection and Implication of Genome Instability in Cancer","volume":"32","author":"Pikor","year":"2013","journal-title":"Cancer Metastasis Rev."},{"key":"B36","doi-asserted-by":"publisher","first-page":"S1","DOI":"10.14639\/0392-100x-suppl.1-40-2020","article-title":"Metastatic Disease in Head & Neck Oncology","volume":"40","author":"Pisani","year":"2020","journal-title":"Acta Otorhinolaryngol. Ital."},{"key":"B37","doi-asserted-by":"publisher","first-page":"742","DOI":"10.1038\/nbt.1914","article-title":"Transcriptome Sequencing across a Prostate Cancer Cohort Identifies PCAT-1, an Unannotated lincRNA Implicated in Disease Progression","volume":"29","author":"Prensner","year":"2011","journal-title":"Nat. Biotechnol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"4951","DOI":"10.1038\/s41598-017-04221-7","article-title":"Somatic Mutations in ZFHX4 Gene Are Associated with Poor Overall Survival of Chinese Esophageal Squamous Cell Carcinoma Patients","volume":"7","author":"Qing","year":"2017","journal-title":"Sci. Rep."},{"key":"B39","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1586\/era.10.6","article-title":"Management of Squamous Cell Carcinoma of the Head and Neck: Updated European Treatment Recommendations","volume":"10","author":"Ramos","year":"2010","journal-title":"Expert Rev. anticancer Ther."},{"key":"B40","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1007\/978-981-10-5203-3_7","article-title":"Long Noncoding RNAs in Cancer and Therapeutic Potential","volume":"1008","author":"Renganathan","year":"2017","journal-title":"Adv. Exp. Med. Biol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1093\/jmcb\/mjq057","article-title":"Genomic Instability and Cancer: an Introduction","volume":"3","author":"Shen","year":"2011","journal-title":"J. Mol. Cel. Biol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"51","DOI":"10.3322\/caac.21384","article-title":"The Global Incidence of Lip, Oral Cavity, and Pharyngeal Cancers by Subsite in 2012","volume":"67","author":"Shield","year":"2017","journal-title":"CA: a Cancer J. clinicians"},{"key":"B43","doi-asserted-by":"publisher","first-page":"1330","DOI":"10.1016\/j.gastro.2003.07.006","article-title":"The Genomic Damage Estimated by Arbitrarily Primed PCR DNA Fingerprinting Is Useful for the Prognosis of Gastric Cancer","volume":"125","author":"Suzuki","year":"2003","journal-title":"Gastroenterology"},{"key":"B44","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1002\/iub.1705","article-title":"miR-191\/DAB2 axis Regulates the Tumorigenicity of Estrogen Receptor-Positive Breast Cancer","volume":"70","author":"Tian","year":"2018","journal-title":"IUBMB Life"},{"key":"B45","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1002\/(sici)1097-0258(19970228)16:4<385:aid-sim380>3.0.co;2-3","article-title":"The Lasso Method for Variable Selection in the Cox Model","volume":"16","author":"Tibshirani","year":"1997","journal-title":"Statist. Med."},{"key":"B46","doi-asserted-by":"publisher","first-page":"644","DOI":"10.1016\/j.cell.2017.01.002","article-title":"Endogenous DNA Damage as a Source of Genomic Instability in Cancer","volume":"168","author":"Tubbs","year":"2017","journal-title":"Cell"},{"key":"B47","doi-asserted-by":"publisher","first-page":"991","DOI":"10.1016\/j.dld.2018.08.002","article-title":"Prognostic Factors in Esophageal Cancer Treated with Curative Intent","volume":"50","author":"Vendrely","year":"2018","journal-title":"Dig. Liver Dis."},{"key":"B48","doi-asserted-by":"publisher","first-page":"14736","DOI":"10.1038\/s41598-017-12259-w","article-title":"The Expression of miRNAs Is Associated with Tumour Genome Instability and Predicts the Outcome of Ovarian Cancer Patients Treated with Platinum Agents","volume":"7","author":"Wang","year":"2017","journal-title":"Sci. Rep."},{"key":"B49","doi-asserted-by":"publisher","first-page":"1575","DOI":"10.3389\/fonc.2019.01575","article-title":"A Novel LncRNA, AC091729.7 Promotes Sinonasal Squamous Cell Carcinomas Proliferation and Invasion through Binding SRSF2","volume":"9","author":"Yu","year":"2019","journal-title":"Front. Oncol."},{"key":"B50","doi-asserted-by":"publisher","first-page":"2936","DOI":"10.1038\/s41388-021-01749-x","article-title":"Energy Stress-Induced Linc01564 Activates the Serine Synthesis Pathway and Facilitates Hepatocellular Carcinogenesis","volume":"40","author":"Zhang","year":"2021","journal-title":"Oncogene"}],"container-title":["Frontiers in Cell and Developmental Biology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2021.787766\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,20]],"date-time":"2022-01-20T07:28:01Z","timestamp":1642663681000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2021.787766\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,20]]},"references-count":50,"alternative-id":["10.3389\/fcell.2021.787766"],"URL":"https:\/\/doi.org\/10.3389\/fcell.2021.787766","relation":{},"ISSN":["2296-634X"],"issn-type":[{"value":"2296-634X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,20]]},"article-number":"787766"}}