{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T21:22:36Z","timestamp":1778620956307,"version":"3.51.4"},"reference-count":46,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T00:00:00Z","timestamp":1760054400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82473376"],"award-info":[{"award-number":["82473376"]}],"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":["2021ZQNZD010"],"award-info":[{"award-number":["2021ZQNZD010"]}],"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":["12374405"],"award-info":[{"award-number":["12374405"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012232","name":"National Key Clinical Specialty Discipline Construction Program of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012232","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003392","name":"Natural Science Foundation of Fujian Province","doi-asserted-by":"publisher","award":["2023J011267"],"award-info":[{"award-number":["2023J011267"]}],"id":[{"id":"10.13039\/501100003392","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003392","name":"Natural Science Foundation of Fujian Province","doi-asserted-by":"publisher","award":["2024J011086"],"award-info":[{"award-number":["2024J011086"]}],"id":[{"id":"10.13039\/501100003392","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003392","name":"Natural Science Foundation of Fujian Province","doi-asserted-by":"publisher","award":["2024J011108"],"award-info":[{"award-number":["2024J011108"]}],"id":[{"id":"10.13039\/501100003392","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["International Immunopharmacology"],"published-print":{"date-parts":[[2025,12]]},"DOI":"10.1016\/j.intimp.2025.115662","type":"journal-article","created":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T15:49:38Z","timestamp":1760543378000},"page":"115662","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"C","title":["PAK6 drives tumor microenvironment remodeling in nasopharyngeal carcinoma with lymph node necrosis: implications for distant metastasis and survival"],"prefix":"10.1016","volume":"167","author":[{"given":"Siqi","family":"Xu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenqian","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiuhua","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Honghong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chaoying","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuhao","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongyuan","family":"Su","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junping","family":"Pan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaochuan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sufang","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.intimp.2025.115662_bb0005","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/S0140-6736(19)30956-0","article-title":"Nasopharyngeal carcinoma","volume":"394","author":"Chen","year":"2019","journal-title":"Lancet"},{"key":"10.1016\/j.intimp.2025.115662_bb0010","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1002\/cncr.20358","article-title":"Lung metastasis alone in nasopharyngeal carcinoma: a relatively favorable prognostic group","volume":"101","author":"Hui","year":"2004","journal-title":"Cancer"},{"key":"10.1016\/j.intimp.2025.115662_bb0015","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.1007\/s11864-023-01101-3","article-title":"Recurrent\/metastatic nasopharyngeal carcinoma treatment from present to future: where are we and where are we heading?","volume":"24","author":"Juarez-Vignon Whaley","year":"2023","journal-title":"Curr. Treat. Options Oncol."},{"key":"10.1016\/j.intimp.2025.115662_bb0020","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1016\/S1470-2045(18)30080-9","article-title":"Development and validation of a gene expression-based signature to predict distant metastasis in locoregionally advanced nasopharyngeal carcinoma: a retrospective, multicentre, cohort study","volume":"19","author":"Tang","year":"2018","journal-title":"Lancet Oncol."},{"key":"10.1016\/j.intimp.2025.115662_bb0025","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1007\/978-3-030-22254-3_2","article-title":"Current perspectives on nasopharyngeal carcinoma","volume":"1164","author":"Lee","year":"2019","journal-title":"Adv. Exp. Med. Biol."},{"key":"10.1016\/j.intimp.2025.115662_bb0030","doi-asserted-by":"crossref","DOI":"10.1259\/bjr.20190244","article-title":"The evolution of nasopharyngeal carcinoma staging","volume":"92","author":"Guo","year":"2019","journal-title":"Br. J. Radiol."},{"key":"10.1016\/j.intimp.2025.115662_bb0035","doi-asserted-by":"crossref","first-page":"3356","DOI":"10.1200\/JCO.2015.60.9347","article-title":"Management of Nasopharyngeal Carcinoma: current practice and future perspective","volume":"33","author":"Lee","year":"2015","journal-title":"J. Clin. Oncol."},{"key":"10.1016\/j.intimp.2025.115662_bb0040","doi-asserted-by":"crossref","first-page":"959","DOI":"10.7150\/jca.17998","article-title":"Influence of cervical node necrosis of different grades on the prognosis of nasopharyngeal carcinoma patients treated with intensity-modulated radiotherapy","volume":"8","author":"Zhang","year":"2017","journal-title":"J. Cancer"},{"key":"10.1016\/j.intimp.2025.115662_bb0045","doi-asserted-by":"crossref","DOI":"10.1016\/j.oraloncology.2020.104864","article-title":"Prognostic value and the potential role of treatment options for cervical lymph node necrosis in nasopharyngeal carcinoma","volume":"109","author":"Liu","year":"2020","journal-title":"Oral Oncol."},{"key":"10.1016\/j.intimp.2025.115662_bb0050","doi-asserted-by":"crossref","unstructured":"M. Lan, Y. Huang, C.-Y. Chen, F. Han, S.-X. Wu, L. Tian, L. Zheng, T.-X. Lu, Prognostic Value of Cervical Nodal Necrosis in Nasopharyngeal Carcinoma: Analysis of 1800 Patients with positive cervical nodal metastasis at MR imaging, Radiology 276 (2015) 536\u2013544. doi:https:\/\/doi.org\/10.1148\/radiol.15141251.","DOI":"10.1148\/radiol.15141251"},{"key":"10.1016\/j.intimp.2025.115662_bb0055","doi-asserted-by":"crossref","first-page":"e18136","DOI":"10.1200\/JCO.2017.35.15_suppl.e18136","article-title":"Lymph node metastasis and prognostic value of NPC based on the UICC lymph node staging for cervical lymph node levels","volume":"35","author":"Lang","year":"2017","journal-title":"JCO"},{"key":"10.1016\/j.intimp.2025.115662_bb0060","doi-asserted-by":"crossref","first-page":"1222","DOI":"10.4143\/crt.2018.595","article-title":"Prognostic Value and staging classification of lymph nodal necrosis in nasopharyngeal carcinoma after intensity-modulated radiotherapy","volume":"51","author":"Feng","year":"2019","journal-title":"Cancer Res. Treat."},{"key":"10.1016\/j.intimp.2025.115662_bb0065","doi-asserted-by":"crossref","DOI":"10.1016\/j.oraloncology.2023.106438","article-title":"Prognostic nomograms for nasopharyngeal carcinoma with nodal features and potential indication for N staging system: validation and comparison of seven N stage schemes","volume":"144","author":"Peng","year":"2023","journal-title":"Oral Oncol."},{"key":"10.1016\/j.intimp.2025.115662_bb0070","doi-asserted-by":"crossref","first-page":"7710","DOI":"10.1007\/s00330-022-08785-5","article-title":"Prognostic value of quantitative cervical nodal necrosis burden on MRI in nasopharyngeal carcinoma and its role as a stratification marker for induction chemotherapy","volume":"32","author":"Li","year":"2022","journal-title":"Eur. Radiol."},{"key":"10.1016\/j.intimp.2025.115662_bb0075","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1016\/j.biomaterials.2018.08.014","article-title":"Hypoxia-responsive block copolymer radiosensitizers as anticancer drug nanocarriers for enhanced chemoradiotherapy of bulky solid tumors","volume":"181","author":"Yin","year":"2018","journal-title":"Biomaterials"},{"key":"10.1016\/j.intimp.2025.115662_bb0080","doi-asserted-by":"crossref","first-page":"2822","DOI":"10.1002\/cam4.1233","article-title":"Combined prognostic value of pretreatment anemia and cervical node necrosis in patients with nasopharyngeal carcinoma receiving intensity-modulated radiotherapy: a large-scale retrospective study","volume":"6","author":"Zhang","year":"2017","journal-title":"Cancer Med."},{"key":"10.1016\/j.intimp.2025.115662_bb0085","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1038\/s41568-022-00531-9","article-title":"Improving head and neck cancer therapies by immunomodulation of the tumour microenvironment","volume":"23","author":"Ruffin","year":"2023","journal-title":"Nat. Rev. Cancer"},{"key":"10.1016\/j.intimp.2025.115662_bb0090","doi-asserted-by":"crossref","first-page":"7338","DOI":"10.1038\/s41467-021-27619-4","article-title":"Investigating immune and non-immune cell interactions in head and neck tumors by single-cell RNA sequencing","volume":"12","author":"K\u00fcrten","year":"2021","journal-title":"Nat. Commun."},{"key":"10.1016\/j.intimp.2025.115662_bb0095","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.semcancer.2018.01.006","article-title":"P21 activated kinase signaling in cancer","volume":"54","author":"Rane","year":"2019","journal-title":"Semin. Cancer Biol."},{"key":"10.1016\/j.intimp.2025.115662_bb0100","doi-asserted-by":"crossref","DOI":"10.1016\/j.bbamcr.2020.118888","article-title":"p21-activated kinase 6 controls mitosis and hepatocellular carcinoma progression by regulating Eg5","volume":"1868","author":"Zheng","year":"2021","journal-title":"Biochim Biophys Acta Mol Cell Res"},{"key":"10.1016\/j.intimp.2025.115662_bb0105","doi-asserted-by":"crossref","first-page":"2387","DOI":"10.3892\/ol.2020.11797","article-title":"PAK6 promotes cervical cancer progression through activation of the Wnt\/\u03b2-catenin signaling pathway","volume":"20","author":"Yang","year":"2020","journal-title":"Oncol. Lett."},{"key":"10.1016\/j.intimp.2025.115662_bb0110","doi-asserted-by":"crossref","first-page":"355","DOI":"10.18632\/oncotarget.2803","article-title":"PAK6 increase chemoresistance and is a prognostic marker for stage II and III colon cancer patients undergoing 5-FU based chemotherapy","volume":"6","author":"Chen","year":"2015","journal-title":"Oncotarget"},{"key":"10.1016\/j.intimp.2025.115662_bb0115","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.jss.2014.01.049","article-title":"Expression and prognostic significance of p21-activated kinase 6 in hepatocellular carcinoma","volume":"189","author":"Chen","year":"2014","journal-title":"J. Surg. Res."},{"key":"10.1016\/j.intimp.2025.115662_bb0120","first-page":"380","article-title":"PAK6 targets to cell-cell adhesions through its N-terminus in a Cdc42-dependent manner to drive epithelial colony escape","volume":"129","author":"Morse","year":"2016","journal-title":"J. Cell Sci."},{"key":"10.1016\/j.intimp.2025.115662_bb0125","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1148\/radiology.177.2.2217772","article-title":"Cervical lymph node metastasis: assessment of radiologic criteria","volume":"177","author":"van den Brekel","year":"1990","journal-title":"Radiology"},{"key":"10.1016\/j.intimp.2025.115662_bb0130","doi-asserted-by":"crossref","first-page":"1572","DOI":"10.1136\/bmj.317.7172.1572","article-title":"Survival probabilities (the Kaplan-Meier method)","volume":"317","author":"Bland","year":"1998","journal-title":"BMJ"},{"key":"10.1016\/j.intimp.2025.115662_bb0135","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gkv007","article-title":"limma powers differential expression analyses for RNA-sequencing and microarray studies","volume":"43","author":"Ritchie","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.intimp.2025.115662_bb0140","doi-asserted-by":"crossref","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":"Stat. Med."},{"key":"10.1016\/j.intimp.2025.115662_bb0145","doi-asserted-by":"crossref","first-page":"D331","DOI":"10.1093\/nar\/gkw1108","article-title":"Expansion of the gene ontology knowledgebase and resources","volume":"45","author":"The Gene Ontology Consortium","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.intimp.2025.115662_bb0150","doi-asserted-by":"crossref","first-page":"D353","DOI":"10.1093\/nar\/gkw1092","article-title":"KEGG: new perspectives on genomes, pathways, diseases and drugs","volume":"45","author":"Kanehisa","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.intimp.2025.115662_bb0155","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1186\/s13059-017-1349-1","article-title":"xCell: digitally portraying the tissue cellular heterogeneity landscape","volume":"18","author":"Aran","year":"2017","journal-title":"Genome Biol."},{"key":"10.1016\/j.intimp.2025.115662_bb0160","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1186\/s13059-016-1070-5","article-title":"Estimating the population abundance of tissue-infiltrating immune and stromal cell populations using gene expression","volume":"17","author":"Becht","year":"2016","journal-title":"Genome Biol."},{"key":"10.1016\/j.intimp.2025.115662_bb0165","doi-asserted-by":"crossref","first-page":"2612","DOI":"10.1038\/ncomms3612","article-title":"Inferring tumour purity and stromal and immune cell admixture from expression data","volume":"4","author":"Yoshihara","year":"2013","journal-title":"Nat. Commun."},{"key":"10.1016\/j.intimp.2025.115662_bb0170","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1016\/j.immuni.2013.10.003","article-title":"Spatiotemporal dynamics of intratumoral immune cells reveal the immune landscape in human cancer","volume":"39","author":"Bindea","year":"2013","journal-title":"Immunity"},{"key":"10.1016\/j.intimp.2025.115662_bb0175","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.radonc.2020.11.011","article-title":"Influence of tumor necrosis on treatment sensitivity and long-term survival in nasopharyngeal carcinoma","volume":"155","author":"Liang","year":"2021","journal-title":"Radiother. Oncol."},{"key":"10.1016\/j.intimp.2025.115662_bb0180","doi-asserted-by":"crossref","first-page":"6841","DOI":"10.1002\/cam4.2481","article-title":"Combining pretreatment plasma Epstein-Barr virus DNA level and cervical node necrosis improves prognostic stratification in patients with nasopharyngeal carcinoma: a cohort study","volume":"8","author":"Du","year":"2019","journal-title":"Cancer Med."},{"key":"10.1016\/j.intimp.2025.115662_bb0185","doi-asserted-by":"crossref","first-page":"7497","DOI":"10.1158\/1078-0432.CCR-08-0271","article-title":"The N staging system in nasopharyngeal carcinoma with radiation therapy oncology group guidelines for lymph node levels based on magnetic resonance imaging","volume":"14","author":"Mao","year":"2008","journal-title":"Clin. Cancer Res."},{"key":"10.1016\/j.intimp.2025.115662_bb0190","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.ebiom.2017.06.028","article-title":"Prognostic and predictive Value of p21-activated kinase 6 associated support vector machine classifier in gastric Cancer treated by 5-fluorouracil\/Oxaliplatin chemotherapy","volume":"22","author":"Jiang","year":"2017","journal-title":"EBioMedicine"},{"key":"10.1016\/j.intimp.2025.115662_bb0195","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1016\/j.urology.2008.09.041","article-title":"Knockdown of p21-activated kinase 6 inhibits prostate cancer growth and enhances chemosensitivity to docetaxel","volume":"73","author":"Wen","year":"2009","journal-title":"Urology"},{"key":"10.1016\/j.intimp.2025.115662_bb0200","doi-asserted-by":"crossref","first-page":"61229","DOI":"10.18632\/oncotarget.11310","article-title":"Chronic exposure to cigarette smoke leads to activation of p21 (RAC1)-activated kinase 6 (PAK6) in non-small cell lung cancer cells","volume":"7","author":"Raja","year":"2016","journal-title":"Oncotarget"},{"key":"10.1016\/j.intimp.2025.115662_bb0205","doi-asserted-by":"crossref","first-page":"19179","DOI":"10.1074\/jbc.M117.808063","article-title":"\u03b21 integrin-dependent Rac\/group I PAK signaling mediates YAP activation of yes-associated protein 1 (YAP1) via NF2\/merlin","volume":"292","author":"Sabra","year":"2017","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.intimp.2025.115662_bb0210","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.gene.2017.12.039","article-title":"Cloning and functional characterization of human Pak1 promoter by steroid hormones","volume":"646","author":"Raghavan","year":"2018","journal-title":"Gene"},{"key":"10.1016\/j.intimp.2025.115662_bb0215","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1186\/s12943-017-0744-2","article-title":"JMJD6 promotes melanoma carcinogenesis through regulation of the alternative splicing of PAK1, a key MAPK signaling component","volume":"16","author":"Liu","year":"2017","journal-title":"Mol. Cancer"},{"key":"10.1016\/j.intimp.2025.115662_bb0220","doi-asserted-by":"crossref","first-page":"1527","DOI":"10.3390\/cancers11101527","article-title":"The PAK1-Stat3 signaling pathway activates IL-6 gene transcription and human breast Cancer stem cell formation","volume":"11","author":"Kim","year":"2019","journal-title":"Cancers (Basel)"},{"key":"10.1016\/j.intimp.2025.115662_bb0225","doi-asserted-by":"crossref","DOI":"10.3389\/fonc.2022.1023177","article-title":"The role of IL-6\/JAK2\/STAT3 signaling pathway in cancers","volume":"12","author":"Huang","year":"2022","journal-title":"Front. Oncol."},{"key":"10.1016\/j.intimp.2025.115662_bb0230","doi-asserted-by":"crossref","DOI":"10.1136\/jitc-2021-003402","article-title":"PI3K activation allows immune evasion by promoting an inhibitory myeloid tumor microenvironment","volume":"10","author":"Collins","year":"2022","journal-title":"J. Immunother. Cancer"}],"container-title":["International Immunopharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1567576925016534?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1567576925016534?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T20:59:12Z","timestamp":1778619552000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1567576925016534"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12]]},"references-count":46,"alternative-id":["S1567576925016534"],"URL":"https:\/\/doi.org\/10.1016\/j.intimp.2025.115662","relation":{},"ISSN":["1567-5769"],"issn-type":[{"value":"1567-5769","type":"print"}],"subject":[],"published":{"date-parts":[[2025,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"PAK6 drives tumor microenvironment remodeling in nasopharyngeal carcinoma with lymph node necrosis: implications for distant metastasis and survival","name":"articletitle","label":"Article Title"},{"value":"International Immunopharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.intimp.2025.115662","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Authors. Published by Elsevier B.V.","name":"copyright","label":"Copyright"}],"article-number":"115662"}}