{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T16:52:51Z","timestamp":1792687971078,"version":"4.5.0"},"reference-count":79,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T00:00:00Z","timestamp":1746489600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T00:00:00Z","timestamp":1746489600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/s41598-025-99017-5","type":"journal-article","created":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T03:40:19Z","timestamp":1746502819000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Integrative bioinformatics and machine learning identify key crosstalk genes and immune interactions in head and neck cancer and Hodgkin lymphoma"],"prefix":"10.1038","volume":"15","author":[{"given":"Meiling","family":"Qin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinxin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xun","family":"Gong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,5,6]]},"reference":[{"key":"99017_CR1","doi-asserted-by":"publisher","first-page":"209","DOI":"10.3322\/caac.21660","volume":"71","author":"H Sung","year":"2021","unstructured":"Sung, H. et al. Global Cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 71, 209\u2013249. https:\/\/doi.org\/10.3322\/caac.21660 (2021).","journal-title":"CA Cancer J. Clin."},{"key":"99017_CR2","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/j.ejca.2021.06.039","volume":"156","author":"Y Guo","year":"2021","unstructured":"Guo, Y. et al. First-line treatment with chemotherapy plus cetuximab in Chinese patients with recurrent and\/or metastatic squamous cell carcinoma of the head and neck: Efficacy and safety results of the randomised, phase III CHANGE-2 trial. Eur. J. Cancer. 156, 35\u201345. https:\/\/doi.org\/10.1016\/j.ejca.2021.06.039 (2021).","journal-title":"Eur. J. Cancer"},{"key":"99017_CR3","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines10102498","author":"D Galizia","year":"2022","unstructured":"Galizia, D. et al. How risk factors affect head and neck squamous cell carcinoma (HNSCC) tumor immune microenvironment (TIME): Their influence on immune escape mechanisms and immunotherapy strategy. Biomedicines https:\/\/doi.org\/10.3390\/biomedicines10102498 (2022).","journal-title":"Biomedicines"},{"key":"99017_CR4","doi-asserted-by":"publisher","first-page":"5725","DOI":"10.21037\/tcr-24-1064","volume":"13","author":"J Zheng","year":"2024","unstructured":"Zheng, J., Li, X., Gong, X., Hu, Y. & Tang, M. Elucidating the molecular and immune interplay between head and neck squamous cell carcinoma and diffuse large B-cell lymphoma through bioinformatics and machine learning. Transl. Cancer Res. 13, 5725\u20135750. https:\/\/doi.org\/10.21037\/tcr-24-1064 (2024).","journal-title":"Transl. Cancer Res."},{"key":"99017_CR5","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1053\/j.seminhematol.2016.05.007","volume":"53","author":"S Mathas","year":"2016","unstructured":"Mathas, S., Hartmann, S. & Kuppers, R. Hodgkin lymphoma: Pathology and biology. Semin. Hematol. 53, 139\u2013147. https:\/\/doi.org\/10.1053\/j.seminhematol.2016.05.007 (2016).","journal-title":"Semin. Hematol."},{"key":"99017_CR6","doi-asserted-by":"publisher","first-page":"1034398","DOI":"10.3389\/fonc.2022.1034398","volume":"12","author":"J Hu","year":"2022","unstructured":"Hu, J., Zhang, X., Tao, H. & Jia, Y. The prognostic value of Epstein\u2013Barr virus infection in Hodgkin lymphoma: A systematic review and meta-analysis. Front. Oncol. 12, 1034398. https:\/\/doi.org\/10.3389\/fonc.2022.1034398 (2022).","journal-title":"Front. Oncol."},{"key":"99017_CR7","doi-asserted-by":"publisher","first-page":"494","DOI":"10.1177\/0194599818770621","volume":"159","author":"SH Kim","year":"2018","unstructured":"Kim, S. H. et al. Differential diagnosis of sinonasal lymphoma and squamous cell carcinoma on CT, MRI, and PET\/CT. Otolaryngol. Head Neck Surg. 159, 494\u2013500. https:\/\/doi.org\/10.1177\/0194599818770621 (2018).","journal-title":"Otolaryngol. Head Neck Surg."},{"key":"99017_CR8","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1016\/j.anl.2008.10.012","volume":"36","author":"YH Joo","year":"2009","unstructured":"Joo, Y. H., Jung, C. K., Sun, D. I. & Kim, M. S. Synchronous laryngeal squamous cell carcinoma and hodgkin lymphoma of the head and neck region. Auris Nasus Larynx. 36, 501\u2013504. https:\/\/doi.org\/10.1016\/j.anl.2008.10.012 (2009).","journal-title":"Auris Nasus Larynx"},{"key":"99017_CR9","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1016\/j.otohns.2007.11.026","volume":"138","author":"MG Moore","year":"2008","unstructured":"Moore, M. G. & Bhattacharyya, N. Survival outcomes for head and neck squamous cell carcinoma arising after lymphoma. Otolaryngol. Head Neck Surg. 138, 388\u2013393. https:\/\/doi.org\/10.1016\/j.otohns.2007.11.026 (2008).","journal-title":"Otolaryngol. Head Neck Surg."},{"key":"99017_CR10","doi-asserted-by":"publisher","first-page":"e0174136","DOI":"10.1371\/journal.pone.0174136","volume":"12","author":"H Takada","year":"2017","unstructured":"Takada, H. et al. EBV induces persistent NF-kappaB activation and contributes to survival of EBV-positive neoplastic T- or NK-cells. PLoS One. 12, e0174136. https:\/\/doi.org\/10.1371\/journal.pone.0174136 (2017).","journal-title":"PLoS One"},{"key":"99017_CR11","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1097\/CEJ.0000000000000554","volume":"29","author":"MH Karbalaie Niya","year":"2020","unstructured":"Karbalaie Niya, M. H. et al. Epstein\u2013Barr virus molecular epidemiology and variants identification in head and neck squamous cell carcinoma. Eur. J. Cancer Prev. 29, 523\u2013530. https:\/\/doi.org\/10.1097\/CEJ.0000000000000554 (2020).","journal-title":"Eur. J. Cancer Prev."},{"key":"99017_CR12","doi-asserted-by":"publisher","first-page":"416","DOI":"10.1002\/1097-0142(197102)27:2<416::AID-CNCR2820270227>3.0.CO;2-W","volume":"27","author":"PH Levine","year":"1971","unstructured":"Levine, P. H. et al. Elevated antibody titers to Epstein\u2013Barr virus in Hodgkin\u2019s disease. Cancer 27, 416\u2013421 (1971).","journal-title":"Cancer"},{"key":"99017_CR13","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1093\/ajcp\/84.3.385","volume":"84","author":"S Poppema","year":"1985","unstructured":"Poppema, S., van Imhoff, G., Torensma, R. & Smit, J. Lymphadenopathy morphologically consistent with Hodgkin\u2019s disease associated with Epstein\u2013Barr virus infection. Am. J. Clin. Pathol. 84, 385\u2013390. https:\/\/doi.org\/10.1093\/ajcp\/84.3.385 (1985).","journal-title":"Am. J. Clin. Pathol."},{"key":"99017_CR14","first-page":"86","volume":"129","author":"LM Weiss","year":"1987","unstructured":"Weiss, L. M., Strickler, J. G., Warnke, R. A., Purtilo, D. T. & Sklar, J. Epstein\u2013Barr viral DNA in tissues of Hodgkin\u2019s disease. Am. J. Pathol. 129, 86\u201391 (1987).","journal-title":"Am. J. Pathol."},{"key":"99017_CR15","doi-asserted-by":"publisher","first-page":"810","DOI":"10.1182\/blood.V74.2.810.810","volume":"74","author":"I Anagnostopoulos","year":"1989","unstructured":"Anagnostopoulos, I., Herbst, H., Niedobitek, G. & Stein, H. Demonstration of monoclonal EBV genomes in Hodgkin\u2019s disease and Ki-1-positive anaplastic large cell lymphoma by combined Southern blot and in situ hybridization. Blood 74, 810\u2013816 (1989).","journal-title":"Blood"},{"key":"99017_CR16","doi-asserted-by":"publisher","first-page":"502","DOI":"10.1056\/nejm198902233200806","volume":"320","author":"LM Weiss","year":"1989","unstructured":"Weiss, L. M., Movahed, L. A., Warnke, R. A. & Sklar, J. Detection of Epstein\u2013Barr viral genomes in Reed\u2013Sternberg cells of Hodgkin\u2019s disease. N. Engl. J. Med. 320, 502\u2013506. https:\/\/doi.org\/10.1056\/nejm198902233200806 (1989).","journal-title":"N. Engl. J. Med."},{"key":"99017_CR17","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1002\/path.1711640404","volume":"164","author":"PJ Coates","year":"1991","unstructured":"Coates, P. J., Slavin, G. & D\u2019Ardenne, A. J. Persistence of Epstein\u2013Barr virus in Reed\u2013Sternberg cells throughout the course of Hodgkin\u2019s disease. J. Pathol. 164, 291\u2013297. https:\/\/doi.org\/10.1002\/path.1711640404 (1991).","journal-title":"J. Pathol."},{"key":"99017_CR18","doi-asserted-by":"publisher","first-page":"2961","DOI":"10.1172\/jci119849","volume":"100","author":"RC Bargou","year":"1997","unstructured":"Bargou, R. C. et al. Constitutive nuclear factor-kappaB-RelA activation is required for proliferation and survival of Hodgkin\u2019s disease tumor cells. J. Clin. Invest. 100, 2961\u20132969. https:\/\/doi.org\/10.1172\/jci119849 (1997).","journal-title":"J. Clin. Invest."},{"key":"99017_CR19","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1002\/path.1725","volume":"205","author":"A Dutton","year":"2005","unstructured":"Dutton, A., Reynolds, G. M., Dawson, C. W., Young, L. S. & Murray, P. G. Constitutive activation of phosphatidyl-inositide 3 kinase contributes to the survival of Hodgkin\u2019s lymphoma cells through a mechanism involving Akt kinase and mTOR. J. Pathol. 205, 498\u2013506. https:\/\/doi.org\/10.1002\/path.1725 (2005).","journal-title":"J. Pathol."},{"key":"99017_CR20","doi-asserted-by":"publisher","first-page":"e1002697","DOI":"10.1371\/journal.ppat.1002697","volume":"8","author":"E Heath","year":"2012","unstructured":"Heath, E. et al. Epstein\u2013Barr virus infection of Na\u00efve B cells in vitro frequently selects clones with mutated Immunoglobulin genotypes: Implications for virus biology. PLoS Pathog. 8, e1002697. https:\/\/doi.org\/10.1371\/journal.ppat.1002697 (2012).","journal-title":"PLoS Pathog"},{"key":"99017_CR21","doi-asserted-by":"publisher","first-page":"936","DOI":"10.1038\/sj.leu.2403750","volume":"19","author":"U Holtick","year":"2005","unstructured":"Holtick, U. et al. STAT3 is essential for hodgkin lymphoma cell proliferation and is a target of tyrphostin AG17 which confers sensitization for apoptosis. Leukemia 19, 936\u2013944. https:\/\/doi.org\/10.1038\/sj.leu.2403750 (2005).","journal-title":"Leukemia"},{"key":"99017_CR22","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14215406","author":"LRC Castellano","year":"2022","unstructured":"Castellano, L. R. C. et al. Implications and emerging therapeutic avenues of inflammatory response in HPV\u2009+\u2009head and neck squamous cell carcinoma. Cancers (Basel). https:\/\/doi.org\/10.3390\/cancers14215406 (2022).","journal-title":"Cancers (Basel)"},{"key":"99017_CR23","doi-asserted-by":"publisher","first-page":"116","DOI":"10.3322\/caac.21438","volume":"68","author":"S Shanbhag","year":"2018","unstructured":"Shanbhag, S. & Ambinder, R. F. Hodgkin lymphoma: A review and update on recent progress. CA Cancer J. Clin. 68, 116\u2013132. https:\/\/doi.org\/10.3322\/caac.21438 (2018).","journal-title":"CA Cancer J. Clin."},{"key":"99017_CR24","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1038\/s41568-022-00531-9","volume":"23","author":"AT Ruffin","year":"2023","unstructured":"Ruffin, A. T. et al. Improving head and neck cancer therapies by Immunomodulation of the tumour microenvironment. Nat. Rev. Cancer. 23, 173\u2013188. https:\/\/doi.org\/10.1038\/s41568-022-00531-9 (2023).","journal-title":"Nat. Rev. Cancer"},{"key":"99017_CR25","doi-asserted-by":"publisher","first-page":"794","DOI":"10.3324\/haematol.2015.132761","volume":"101","author":"S Vardhana","year":"2016","unstructured":"Vardhana, S. & Younes, A. The immune microenvironment in hodgkin lymphoma: T cells, B cells, and immune checkpoints. Haematologica 101, 794\u2013802. https:\/\/doi.org\/10.3324\/haematol.2015.132761 (2016).","journal-title":"Haematologica"},{"key":"99017_CR26","doi-asserted-by":"publisher","first-page":"1436","DOI":"10.1002\/cncr.29231","volume":"121","author":"AK Chowdhry","year":"2015","unstructured":"Chowdhry, A. K. et al. Second primary head and neck cancer after hodgkin lymphoma: A population-based study of 44,879 survivors of hodgkin lymphoma. Cancer 121, 1436\u20131445. https:\/\/doi.org\/10.1002\/cncr.29231 (2015).","journal-title":"Cancer"},{"key":"99017_CR27","doi-asserted-by":"publisher","first-page":"2499","DOI":"10.1056\/NEJMoa1505949","volume":"373","author":"M Schaapveld","year":"2015","unstructured":"Schaapveld, M. et al. Second cancer risk up to 40 years after treatment for Hodgkin\u2019s lymphoma. N. Engl. J. Med. 373, 2499\u20132511. https:\/\/doi.org\/10.1056\/NEJMoa1505949 (2015).","journal-title":"N. Engl. J. Med."},{"key":"99017_CR28","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20102416","author":"D Aldinucci","year":"2019","unstructured":"Aldinucci, D., Borghese, C. & Casagrande, N. Formation of the immunosuppressive microenvironment of classic hodgkin lymphoma and therapeutic approaches to counter it. Int. J. Mol. Sci. https:\/\/doi.org\/10.3390\/ijms20102416 (2019).","journal-title":"Int. J. Mol. Sci."},{"key":"99017_CR29","doi-asserted-by":"publisher","first-page":"A68","DOI":"10.5114\/wo.2014.47136","volume":"19","author":"K Tomczak","year":"2015","unstructured":"Tomczak, K., Czerwinska, P. & Wiznerowicz, M. The Cancer Genome Atlas (TCGA): An immeasurable source of knowledge. Contemp. Oncol. (Pozn). 19, A68\u2013A77. https:\/\/doi.org\/10.5114\/wo.2014.47136 (2015).","journal-title":"Contemp. Oncol. (Pozn)"},{"key":"99017_CR30","doi-asserted-by":"publisher","first-page":"D991","DOI":"10.1093\/nar\/gks1193","volume":"41","author":"T Barrett","year":"2013","unstructured":"Barrett, T. et al. NCBI GEO: Archive for functional genomics data sets\u2014Update. Nucleic Acids Res. 41, D991\u2013D995. https:\/\/doi.org\/10.1093\/nar\/gks1193 (2013).","journal-title":"Nucleic Acids Res."},{"key":"99017_CR31","doi-asserted-by":"publisher","first-page":"2251","DOI":"10.1084\/jem.20080809","volume":"205","author":"V Brune","year":"2008","unstructured":"Brune, V. et al. Origin and pathogenesis of nodular lymphocyte-predominant hodgkin lymphoma as revealed by global gene expression analysis. J. Exp. Med. 205, 2251\u20132268. https:\/\/doi.org\/10.1084\/jem.20080809 (2008).","journal-title":"J. Exp. Med."},{"key":"99017_CR32","doi-asserted-by":"publisher","first-page":"2996","DOI":"10.1172\/JCI95993","volume":"128","author":"MA Weniger","year":"2018","unstructured":"Weniger, M. A. et al. Human CD30+\u2009B cells represent a unique subset related to hodgkin lymphoma cells. J. Clin. Investig. 128, 2996\u20133007. https:\/\/doi.org\/10.1172\/JCI95993 (2018).","journal-title":"J. Clin. Investig"},{"key":"99017_CR33","doi-asserted-by":"publisher","first-page":"788580","DOI":"10.3389\/fgene.2022.788580","volume":"13","author":"Y Zhao","year":"2022","unstructured":"Zhao, Y. et al. Comprehensive analysis of tumor immune microenvironment characteristics for the prognostic prediction and immunotherapy of oral squamous cell carcinoma. Front. Genet. 13, 788580. https:\/\/doi.org\/10.3389\/fgene.2022.788580 (2022).","journal-title":"Front. Genet."},{"key":"99017_CR34","doi-asserted-by":"publisher","first-page":"2152","DOI":"10.1158\/1055-9965.EPI-07-2893","volume":"17","author":"C Chen","year":"2008","unstructured":"Chen, C. et al. Gene expression profiling identifies genes predictive of oral squamous cell carcinoma. Cancer Epidemiol. Biomark. Prev. 17, 2152\u20132162. https:\/\/doi.org\/10.1158\/1055-9965.EPI-07-2893 (2008).","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"99017_CR35","doi-asserted-by":"publisher","first-page":"1197","DOI":"10.1158\/1078-0432.CCR-12-2647","volume":"19","author":"P Lohavanichbutr","year":"2013","unstructured":"Lohavanichbutr, P. et al. A 13-gene signature prognostic of HPV-negative OSCC: Discovery and external validation. Clin. Cancer Res. 19, 1197\u20131203. https:\/\/doi.org\/10.1158\/1078-0432.CCR-12-2647 (2013).","journal-title":"Clin. Cancer Res."},{"key":"99017_CR36","doi-asserted-by":"publisher","first-page":"e84928","DOI":"10.1371\/journal.pone.0084928","volume":"8","author":"M Giefing","year":"2013","unstructured":"Giefing, M. et al. Hodgkin\u2013Reed\u2013Sternberg cells in classical hodgkin lymphoma show alterations of genes encoding the NADPH oxidase complex and impaired reactive oxygen species synthesis capacity. PloS One. 8, e84928. https:\/\/doi.org\/10.1371\/journal.pone.0084928 (2013).","journal-title":"PloS One"},{"key":"99017_CR37","doi-asserted-by":"publisher","DOI":"10.3390\/ijms232315433","author":"Y Xi","year":"2022","unstructured":"Xi, Y. et al. GOLM1 and FAM49B: Potential biomarkers in HNSCC based on bioinformatics and immunohistochemical analysis. Int. J. Mol. Sci. https:\/\/doi.org\/10.3390\/ijms232315433 (2022).","journal-title":"Int. J. Mol. Sci."},{"key":"99017_CR38","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1186\/1471-2164-9-69","volume":"9","author":"H Ye","year":"2008","unstructured":"Ye, H. et al. Transcriptomic dissection of tongue squamous cell carcinoma. BMC Genom. 9, 69. https:\/\/doi.org\/10.1186\/1471-2164-9-69 (2008).","journal-title":"BMC Genom."},{"key":"99017_CR39","doi-asserted-by":"publisher","first-page":"875","DOI":"10.1002\/jcp.24816","volume":"230","author":"CH Lee","year":"2015","unstructured":"Lee, C. H. et al. IL-1beta promotes malignant transformation and tumor aggressiveness in oral cancer. J. Cell. Physiol. 230, 875\u2013884. https:\/\/doi.org\/10.1002\/jcp.24816 (2015).","journal-title":"J. Cell. Physiol."},{"key":"99017_CR40","doi-asserted-by":"publisher","first-page":"1375","DOI":"10.1038\/onc.2013.98","volume":"33","author":"JJ Sheu","year":"2014","unstructured":"Sheu, J. J. et al. LRIG1 modulates aggressiveness of head and neck cancers by regulating EGFR-MAPK-SPHK1 signaling and extracellular matrix remodeling. Oncogene 33, 1375\u20131384. https:\/\/doi.org\/10.1038\/onc.2013.98 (2014).","journal-title":"Oncogene"},{"key":"99017_CR41","doi-asserted-by":"publisher","first-page":"D638","DOI":"10.1093\/nar\/gkac1000","volume":"51","author":"D Szklarczyk","year":"2023","unstructured":"Szklarczyk, D. et al. The STRING database in 2023: Protein\u2013protein association networks and functional enrichment analyses for any sequenced genome of interest. Nucleic Acids Res. 51, D638\u2013D646. https:\/\/doi.org\/10.1093\/nar\/gkac1000 (2023).","journal-title":"Nucleic Acids Res."},{"key":"99017_CR42","doi-asserted-by":"publisher","first-page":"W556","DOI":"10.1093\/nar\/gkz430","volume":"47","author":"Z Tang","year":"2019","unstructured":"Tang, Z., Kang, B., Li, C., Chen, T. & Zhang, Z. GEPIA2: An enhanced web server for large-scale expression profiling and interactive analysis. Nucleic Acids Res. 47, W556\u2013W560. https:\/\/doi.org\/10.1093\/nar\/gkz430 (2019).","journal-title":"Nucleic Acids Res."},{"key":"99017_CR43","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1002\/pro.3307","volume":"27","author":"PJ Thul","year":"2018","unstructured":"Thul, P. J. & Lindskog, C. The human protein atlas: A spatial map of the human proteome. Protein Sci. 27, 233\u2013244. https:\/\/doi.org\/10.1002\/pro.3307 (2018).","journal-title":"Protein Sci."},{"key":"99017_CR44","doi-asserted-by":"publisher","first-page":"W234","DOI":"10.1093\/nar\/gkz240","volume":"47","author":"G Zhou","year":"2019","unstructured":"Zhou, G. et al. NetworkAnalyst 3.0: A visual analytics platform for comprehensive gene expression profiling and meta-analysis. Nucleic Acids Res. 47, W234\u2013W241. https:\/\/doi.org\/10.1093\/nar\/gkz240 (2019).","journal-title":"Nucleic Acids Res."},{"key":"99017_CR45","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1016\/j.neo.2017.05.002650","volume":"19","author":"DS Chandrashekar","year":"2017","unstructured":"Chandrashekar, D. S. et al. UALCAN- A portal for facilitating tumor subgroup gene expression and survival analyses. Neoplasia 19, 649\u2013658. https:\/\/doi.org\/10.1016\/j.neo.2017.05.002650 (2017).","journal-title":"Neoplasia"},{"key":"99017_CR46","doi-asserted-by":"publisher","first-page":"D900","DOI":"10.1093\/nar\/gky939","volume":"47","author":"H Yuan","year":"2019","unstructured":"Yuan, H. et al. CancerSEA: A cancer single-cell state atlas. Nucleic Acids Res. 47, D900\u2013D908. https:\/\/doi.org\/10.1093\/nar\/gky939 (2019).","journal-title":"Nucleic Acids Res."},{"key":"99017_CR47","doi-asserted-by":"publisher","DOI":"10.1093\/bib\/bbac558","author":"CJ Liu","year":"2023","unstructured":"Liu, C. J. et al. GSCA: An integrated platform for gene set cancer analysis at genomic, pharmacogenomic and immunogenomic levels. Brief. Bioinform. https:\/\/doi.org\/10.1093\/bib\/bbac558 (2023).","journal-title":"Brief. Bioinform"},{"key":"99017_CR48","doi-asserted-by":"publisher","first-page":"D1265","DOI":"10.1093\/nar\/gkad976","volume":"52","author":"C Knox","year":"2024","unstructured":"Knox, C. et al. DrugBank 6.0: The drugbank knowledgebase for 2024. Nucleic Acids Res. 52, D1265\u2013D1275. https:\/\/doi.org\/10.1093\/nar\/gkad976 (2024).","journal-title":"Nucleic Acids Res."},{"key":"99017_CR49","doi-asserted-by":"publisher","first-page":"D1227","DOI":"10.1093\/nar\/gkad1040","volume":"52","author":"M Cannon","year":"2024","unstructured":"Cannon, M. et al. DGIdb 5.0: Rebuilding the drug-gene interaction database for precision medicine and drug discovery platforms. Nucleic Acids Res. 52, D1227\u2013D1235. https:\/\/doi.org\/10.1093\/nar\/gkad1040 (2024).","journal-title":"Nucleic Acids Res."},{"key":"99017_CR50","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1038\/nmeth.3337","volume":"12","author":"AM Newman","year":"2015","unstructured":"Newman, A. M. et al. Robust enumeration of cell subsets from tissue expression profiles. Nat. Methods. 12, 453\u2013457. https:\/\/doi.org\/10.1038\/nmeth.3337 (2015).","journal-title":"Nat. Methods"},{"key":"99017_CR51","doi-asserted-by":"publisher","first-page":"e108","DOI":"10.1158\/0008-5472.CAN-17-0307","volume":"77","author":"T Li","year":"2017","unstructured":"Li, T. et al. A web server for comprehensive analysis of tumor-infiltrating immune cells. Cancer Res. 77, e108\u2013e110. https:\/\/doi.org\/10.1158\/0008-5472.CAN-17-0307 (2017).","journal-title":"Cancer Res."},{"key":"99017_CR52","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","volume":"15","author":"MI Love","year":"2014","unstructured":"Love, M. I., Huber, W. & Anders, S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 15, 550. https:\/\/doi.org\/10.1186\/s13059-014-0550-8 (2014).","journal-title":"Genome Biol."},{"key":"99017_CR53","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1089\/omi.2011.0118","volume":"16","author":"G Yu","year":"2012","unstructured":"Yu, G., Wang, L. G., Han, Y. & He, Q. Y. ClusterProfiler: An R package for comparing biological themes among gene clusters. OMICS 16, 284\u2013287. https:\/\/doi.org\/10.1089\/omi.2011.0118 (2012).","journal-title":"OMICS"},{"key":"99017_CR54","doi-asserted-by":"publisher","first-page":"1947","DOI":"10.1002\/pro.3715","volume":"28","author":"M Kanehisa","year":"2019","unstructured":"Kanehisa, M. Toward understanding the origin and evolution of cellular organisms. Protein Sci. 28, 1947\u20131951. https:\/\/doi.org\/10.1002\/pro.3715 (2019).","journal-title":"Protein Sci."},{"key":"99017_CR55","doi-asserted-by":"publisher","first-page":"D672","DOI":"10.1093\/nar\/gkae909","volume":"53","author":"M Kanehisa","year":"2025","unstructured":"Kanehisa, M., Furumichi, M., Sato, Y., Matsuura, Y. & Ishiguro-Watanabe, M. KEGG: Biological systems database as a model of the real world. Nucleic Acids Res. 53, D672\u2013D677. https:\/\/doi.org\/10.1093\/nar\/gkae909 (2025).","journal-title":"Nucleic Acids Res."},{"key":"99017_CR56","doi-asserted-by":"publisher","first-page":"D1036","DOI":"10.1093\/nar\/gkv1165","volume":"44","author":"AH Wagner","year":"2016","unstructured":"Wagner, A. H. et al. DGIdb 2.0: Mining clinically relevant drug-gene interactions. Nucleic Acids Res. 44, D1036\u20131044. https:\/\/doi.org\/10.1093\/nar\/gkv1165 (2016).","journal-title":"Nucleic Acids Res."},{"key":"99017_CR57","doi-asserted-by":"publisher","first-page":"S3","DOI":"10.1007\/s00259-003-1154-9","volume":"30","author":"AJ Swerdlow","year":"2003","unstructured":"Swerdlow, A. J. Epidemiology of Hodgkin\u2019s disease and non-Hodgkin\u2019s lymphoma. Eur. J. Nucl. Med. Mol. Imaging. 30, S3\u2013S12. https:\/\/doi.org\/10.1007\/s00259-003-1154-9 (2003).","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"99017_CR58","doi-asserted-by":"publisher","first-page":"1097","DOI":"10.1016\/j.oraloncology.2013.09.001","volume":"49","author":"HS van Monsjou","year":"2013","unstructured":"van Monsjou, H. S., Wreesmann, V. B., van den Brekel, M. W. & Balm, A. J. Head and neck squamous cell carcinoma in young patients. Oral Oncol. 49, 1097\u20131102. https:\/\/doi.org\/10.1016\/j.oraloncology.2013.09.001 (2013).","journal-title":"Oral Oncol."},{"key":"99017_CR59","doi-asserted-by":"publisher","first-page":"412","DOI":"10.1016\/j.ccell.2020.06.007","volume":"38","author":"R Siersb\u00e6k","year":"2020","unstructured":"Siersb\u00e6k, R. et al. IL6\/STAT3 signaling hijacks estrogen receptor \u03b1 enhancers to drive breast cancer metastasis. Cancer Cell 38, 412\u2013423e419. https:\/\/doi.org\/10.1016\/j.ccell.2020.06.007 (2020).","journal-title":"Cancer Cell"},{"key":"99017_CR60","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1186\/s13046-024-02989-x","volume":"43","author":"Z Hu","year":"2024","unstructured":"Hu, Z. et al. IL6-STAT3-C\/EBP\u03b2-IL6 positive feedback loop in tumor-associated macrophages promotes the EMT and metastasis of lung adenocarcinoma. J. Exp. Clin. Cancer Res. 43, 63. https:\/\/doi.org\/10.1186\/s13046-024-02989-x (2024).","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"99017_CR61","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1289\/ehp.1409437","volume":"124","author":"S Leng","year":"2016","unstructured":"Leng, S. et al. Radon exposure, IL-6 promoter variants, and lung squamous cell carcinoma in former uranium miners. Environ. Health Perspect. 124, 445\u2013451. https:\/\/doi.org\/10.1289\/ehp.1409437 (2016).","journal-title":"Environ. Health Perspect."},{"key":"99017_CR62","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1111\/odi.13751","volume":"28","author":"H Li","year":"2022","unstructured":"Li, H. et al. Andrographolide-loaded solid lipid nanoparticles enhance anti-cancer activity against head and neck cancer and precancerous cells. Oral Dis. 28, 142\u2013149. https:\/\/doi.org\/10.1111\/odi.13751 (2022).","journal-title":"Oral Dis."},{"key":"99017_CR63","doi-asserted-by":"publisher","first-page":"50","DOI":"10.21053\/ceo.2019.00906","volume":"14","author":"U Uz","year":"2021","unstructured":"Uz, U. & Eskiizmir, G. Association between interleukin-6 and head and neck squamous cell carcinoma: A systematic review. Clin. Exp. Otorhinolaryngol. 14, 50\u201360. https:\/\/doi.org\/10.21053\/ceo.2019.00906 (2021).","journal-title":"Clin. Exp. Otorhinolaryngol."},{"key":"99017_CR64","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1016\/j.canlet.2021.12.011","volume":"527","author":"M Li","year":"2022","unstructured":"Li, M., Jin, S., Zhang, Z., Ma, H. & Yang, X. Interleukin-6 facilitates tumor progression by inducing ferroptosis resistance in head and neck squamous cell carcinoma. Cancer Lett. 527, 28\u201340. https:\/\/doi.org\/10.1016\/j.canlet.2021.12.011 (2022).","journal-title":"Cancer Lett."},{"key":"99017_CR65","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1111\/j.1365-2184.2011.00757.x","volume":"44","author":"CP El-Haibi","year":"2011","unstructured":"El-Haibi, C. P., Singh, R., Sharma, P. K., Singh, S. & Lillard, J. W. Jr. CXCL13 mediates prostate cancer cell proliferation through JNK signalling and invasion through ERK activation. Cell. Prolif. 44, 311\u2013319. https:\/\/doi.org\/10.1111\/j.1365-2184.2011.00757.x (2011).","journal-title":"Cell. Prolif."},{"key":"99017_CR66","doi-asserted-by":"publisher","first-page":"2905","DOI":"10.1158\/1078-0432.CCR-06-1670","volume":"13","author":"A Vachani","year":"2007","unstructured":"Vachani, A. et al. A 10-gene classifier for distinguishing head and neck squamous cell carcinoma and lung squamous cell carcinoma. Clin. Cancer Res. 13, 2905\u20132915. https:\/\/doi.org\/10.1158\/1078-0432.CCR-06-1670 (2007).","journal-title":"Clin. Cancer Res."},{"key":"99017_CR67","doi-asserted-by":"publisher","first-page":"107416","DOI":"10.1016\/j.intimp.2021.107416","volume":"94","author":"C Tian","year":"2021","unstructured":"Tian, C. et al. Identification of CXCL13\/CXCR5 Axis\u2019s crucial and complex effect in human lung adenocarcinoma. Int. Immunopharmacol. 94, 107416. https:\/\/doi.org\/10.1016\/j.intimp.2021.107416 (2021).","journal-title":"Int. Immunopharmacol."},{"key":"99017_CR68","doi-asserted-by":"publisher","first-page":"850998","DOI":"10.3389\/fimmu.2022.850998","volume":"13","author":"Z Pan","year":"2022","unstructured":"Pan, Z., Zhu, T., Liu, Y. & Zhang, N. Role of the CXCL13\/CXCR5 axis in autoimmune diseases. Front. Immunol. 13, 850998. https:\/\/doi.org\/10.3389\/fimmu.2022.850998 (2022).","journal-title":"Front. Immunol."},{"key":"99017_CR69","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1186\/s12885-022-09258-0","volume":"22","author":"CY Hsieh","year":"2022","unstructured":"Hsieh, C. Y. et al. Rituximab in combination with gemcitabine plus cisplatin in patients with recurrent and metastatic head and neck squamous cell carcinoma: A phase I trial. BMC Cancer 22, 169. https:\/\/doi.org\/10.1186\/s12885-022-09258-0 (2022).","journal-title":"BMC Cancer"},{"key":"99017_CR70","doi-asserted-by":"publisher","first-page":"1381","DOI":"10.1002\/cbin.12025","volume":"47","author":"MD Hu","year":"2023","unstructured":"Hu, M. D., Jia, L. H. & Wang, M. L. PLAU contributes to the development of cholangiocarcinoma via activating NF-\u03baB signaling pathway. Cell. Biol. Int. 47, 1381\u20131391. https:\/\/doi.org\/10.1002\/cbin.12025 (2023).","journal-title":"Cell. Biol. Int."},{"key":"99017_CR71","doi-asserted-by":"publisher","first-page":"788","DOI":"10.7150\/jca.37323","volume":"11","author":"C Ai","year":"2020","unstructured":"Ai, C. et al. FOXM1 functions collaboratively with PLAU to promote gastric cancer progression. J. Cancer. 11, 788\u2013794. https:\/\/doi.org\/10.7150\/jca.37323 (2020).","journal-title":"J. Cancer"},{"key":"99017_CR72","doi-asserted-by":"publisher","DOI":"10.3892\/or.2022.8462","author":"Y Gao","year":"2023","unstructured":"Gao, Y., Ma, X., Lu, H., Xu, P. & Xu, C. PLAU is associated with cell migration and invasion and is regulated by transcription factor YY1 in cervical cancer. Oncol. Rep. https:\/\/doi.org\/10.3892\/or.2022.8462 (2023).","journal-title":"Oncol. Rep."},{"key":"99017_CR73","doi-asserted-by":"publisher","first-page":"651882","DOI":"10.3389\/fgene.2021.651882","volume":"12","author":"G Chen","year":"2021","unstructured":"Chen, G. et al. PLAU promotes cell proliferation and epithelial-mesenchymal transition in head and neck squamous cell carcinoma. Front. Genet. 12, 651882. https:\/\/doi.org\/10.3389\/fgene.2021.651882 (2021).","journal-title":"Front. Genet."},{"key":"99017_CR74","doi-asserted-by":"publisher","first-page":"1148","DOI":"10.1038\/s41590-022-01267-2","volume":"23","author":"A Christofides","year":"2022","unstructured":"Christofides, A. et al. The complex role of tumor-infiltrating macrophages. Nat. Immunol. 23, 1148\u20131156. https:\/\/doi.org\/10.1038\/s41590-022-01267-2 (2022).","journal-title":"Nat. Immunol."},{"key":"99017_CR75","doi-asserted-by":"publisher","first-page":"680","DOI":"10.1038\/sj.bjp.0706105","volume":"144","author":"MA Hidalgo","year":"2005","unstructured":"Hidalgo, M. A. et al. Andrographolide interferes with binding of nuclear factor-kappaB to DNA in HL-60-derived neutrophilic cells. Br. J. Pharmacol. 144, 680\u2013686. https:\/\/doi.org\/10.1038\/sj.bjp.0706105 (2005).","journal-title":"Br. J. Pharmacol."},{"key":"99017_CR76","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1093\/rheumatology\/keq337","volume":"50","author":"S Rosengren","year":"2011","unstructured":"Rosengren, S., Wei, N., Kalunian, K. C., Kavanaugh, A. & Boyle, D. L. CXCL13: A novel biomarker of B-cell return following rituximab treatment and synovitis in patients with rheumatoid arthritis. Rheumatology (Oxford) 50, 603\u2013610. https:\/\/doi.org\/10.1093\/rheumatology\/keq337 (2011).","journal-title":"Rheumatology (Oxford)"},{"key":"99017_CR77","first-page":"73","volume":"43","author":"RL Sparks","year":"1983","unstructured":"Sparks, R. L., Pool, T. B., Smith, N. K. R. & Cameron, I. L. Effects of amiloride on tumor growth and intracellular element content of tumor cells in vivo. Cancer Res. 43, 73\u201377 (1983).","journal-title":"Cancer Res."},{"key":"99017_CR78","doi-asserted-by":"publisher","first-page":"167533","DOI":"10.1016\/j.jmb.2022.167533","volume":"434","author":"CD Ellson","year":"2022","unstructured":"Ellson, C. D. et al. An integrated pharmacological, structural, and genetic analysis of extracellular versus intracellular ROS production in neutrophils. J. Mol. Biol. 434, 167533. https:\/\/doi.org\/10.1016\/j.jmb.2022.167533 (2022).","journal-title":"J. Mol. Biol."},{"key":"99017_CR79","doi-asserted-by":"publisher","first-page":"2846","DOI":"10.1002\/ijc.29649","volume":"137","author":"G Wichmann","year":"2023","unstructured":"Wichmann, G. et al. The role of HPV RNA transcription, immune response-related gene expression and disruptive TP53 mutations in diagnostic and prognostic profiling of head and neck cancer. Int. J. Cancer. 137, 2846\u20132857 (2023).","journal-title":"Int. J. Cancer"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-99017-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-99017-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-99017-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T03:40:20Z","timestamp":1746502820000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-99017-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,6]]},"references-count":79,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["99017"],"URL":"https:\/\/doi.org\/10.1038\/s41598-025-99017-5","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,6]]},"assertion":[{"value":"9 December 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 April 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 May 2025","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 authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"All authors confirm that they have thoroughly reviewed and approved the final manuscript for publication. As the study does not involve any personal or identifiable data, obtaining individual consent for publication is not applicable. The authors further declare that this work is entirely original and has not been previously published or submitted to any other journal.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"All datasets were downloaded from the public GEO database and TCGA database without restriction. Ethical approval and consent to participate are not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval and consent to participate"}}],"article-number":"15745"}}