{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T08:45:39Z","timestamp":1778057139341,"version":"3.51.4"},"reference-count":37,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2018,9,24]],"date-time":"2018-09-24T00:00:00Z","timestamp":1537747200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Laryngoscope"],"published-print":{"date-parts":[[2019,1]]},"abstract":"<jats:sec><jats:title>Objectives\/Hypothesis<\/jats:title><jats:p>Gene expression analyses of head and neck cancer have revealed four molecular subtypes: basal (BA), mesenchymal (MS), atypical (AT), and classical (CL). We evaluate whether gene expression subtypes in oral cavity squamous cell carcinoma (OCSCC) and laryngeal squamous cell carcinoma (LSCC) can be used to predict nodal metastasis and prognosticate survival.<\/jats:p><\/jats:sec><jats:sec><jats:title>Study Design<\/jats:title><jats:p>Retrospective cohort study and genomic analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>OCSCC and LSCC cases were identified from the The Cancer Genome Atlas (TCGA) head and neck cancer cohort. RNA\u2010seq by expected maximization (RSEM) was used to quantify gene expression levels from TCGA RNA\u2010seq data and to assign each case to one of four subtypes. Descriptive statistics were used to describe patient, disease, and treatment characteristics in each subtype. Cox regression and Kaplan\u2010Meier analyses were used to determine associations with survival.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>OCSCC cases were comprised primarily of the MS and BA subtypes, whereas LSCC was comprised primarily of CL and AT subtypes. In OCSCC, the MS subtype was significantly associated with higher risk of nodal metastasis. In a subset analysis of clinically T1\u20102N0M0 OCSCC, we demonstrate that the MS subtype was predictive of occult nodal metastasis (relative risk\u2009=\u20093.38, 95% confidence interval [CI]: 1.08\u201010.69). In LSCC, the CL subtype was associated with significantly worse overall survival (hazard ratio\u2009=\u20094.32, 95% CI: 1.77\u201010.54, <jats:italic>P<\/jats:italic>\u2009=\u2009.001).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Gene expression analysis reveals potential novel markers of nodal metastasis and survival in human papillomavirus\u2013negative head and neck cancer. Future studies will continue to refine and validate these markers, with the goal of providing molecular risk assessments that guide therapy and improve patient outcomes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Level of Evidence<\/jats:title><jats:p>2b <jats:italic>Laryngoscope<\/jats:italic>, 129:154\u2013161, 2019<\/jats:p><\/jats:sec>","DOI":"10.1002\/lary.27340","type":"journal-article","created":{"date-parts":[[2018,9,24]],"date-time":"2018-09-24T13:05:39Z","timestamp":1537794339000},"page":"154-161","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Gene Expression Subtype Predicts Nodal Metastasis and Survival in Human Papillomavirus\u2013Negative Head and Neck Cancer"],"prefix":"10.1002","volume":"129","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9111-6767","authenticated-orcid":false,"given":"Jose P.","family":"Zevallos","sequence":"first","affiliation":[{"name":"Department of Otolaryngology\u2013Head and Neck Surgery Washington University School of Medicine in St. Louis  St. Louis Missouri"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela L.","family":"Mazul","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2013Head and Neck Surgery Washington University School of Medicine in St. Louis  St. Louis Missouri"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vonn","family":"Walter","sequence":"additional","affiliation":[{"name":"Penn State Hershey Institute for Personalized Medicine  Hershey Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David Neil","family":"Hayes","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology University of Tennessee Health Sciences West Cancer Center  Memphis Tennessee U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,9,24]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/canjclin.55.2.74"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21387"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0912217"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.27727"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2009-0289"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2011.06.013"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1506007"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1067\/mhn.2001.116188"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-10-0199"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1535-6108(04)00112-6"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0056823"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature14129"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-14-2481"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joms.2011.06.212"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10585-014-9690-1"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.28404"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.10.044"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-12-323"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btq170"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-12-0537"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.23410"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0178581"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep18073"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms151221621"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2012.10.001"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2008.12.008"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-07-5003"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2008.06.082"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-13-1655"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-12-4400"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/hed.23663"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1245\/s10434-014-3600-2"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-015-1008-4"},{"key":"e_1_2_8_35_1","first-page":"13235","article-title":"Correlation between expression of NF\u2010E2\u2010related factor 2 and progression of gastric cancer [retracted in: Int J Clin Exp Med 2017;10:1733]","volume":"8","author":"Bao J","year":"2015","journal-title":"Int J Clin Exp Med"},{"key":"e_1_2_8_36_1","first-page":"1502","article-title":"Nrf2 induces cisplatin resistance through activation of autophagy in ovarian carcinoma","volume":"7","author":"Bao LJ","year":"2014","journal-title":"Int J Clin Exp Pathol"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1208285"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.18692"}],"container-title":["The Laryngoscope"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Flary.27340","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/lary.27340","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,14]],"date-time":"2023-09-14T04:34:51Z","timestamp":1694666091000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/lary.27340"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,9,24]]},"references-count":37,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2019,1]]}},"alternative-id":["10.1002\/lary.27340"],"URL":"https:\/\/doi.org\/10.1002\/lary.27340","archive":["Portico"],"relation":{},"ISSN":["0023-852X","1531-4995"],"issn-type":[{"value":"0023-852X","type":"print"},{"value":"1531-4995","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,9,24]]},"assertion":[{"value":"2018-05-11","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-09-24","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}