{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T05:55:47Z","timestamp":1791266147247,"version":"4.1.0"},"reference-count":48,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:00:00Z","timestamp":1791158400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:00:00Z","timestamp":1791158400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82572656"],"award-info":[{"award-number":["82572656"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl Journal of Cancer"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>We aimed to comprehensively evaluate the associations of a broad panel of systemic inflammation\u2010related biomarkers with overall survival (OS) in metastatic nasopharyngeal carcinoma (mNPC) and to assess whether these signatures mediate the adverse impact of high EBV DNA burden on long\u2010term outcomes. This study included 1847 patients with mNPC treated at Sun Yat\u2010sen University Cancer Center between 2016 and 2022. Multivariable Cox proportional hazards models, restricted cubic spline (RCS) models, and time\u2010dependent receiver operating characteristic (ROC) curve analyses were used to evaluate associations of inflammation\u2010related indices with OS. Exploratory mediation analyses quantified the extent to which biomarkers partially mediated the association between plasma EBV DNA burden and mortality risk. Mean follow\u2010up was 45.4\u2009months; 713 (38.6%) deaths occurred. Plasma EBV DNA showed stable discrimination (AUCs of 0.63, 0.62, and 0.61 for 1\u2010, 3\u2010, and 5\u2010year OS). After full adjustment, CALLY and LCR were protective, whereas CAR, NAR, SIRI, IBI, MLR, NC, PC, GPS, mGPS, and LCS were adverse. CAR, CALLY, LCR, IBI, and NC showed the highest discrimination (1\u2010year AUCs, 0.65\u20130.66). Mediation analyses indicated that MLR, SIRI, CALLY, and NC accounted for 7.6%\u20139.6% of the EBV DNA load\u2010mortality association. Elevated pretreatment EBV DNA was associated with a coordinated systemic inflammatory profile and worse OS in mNPC. Selected inflammatory markers statistically accounted for a modest proportion of the observed association between EBV DNA burden and mortality. Integrating EBV DNA with inflammatory profiles may improve risk stratification and guide intensified surveillance, earlier assessment, and risk\u2010adapted therapy.<\/jats:p>","DOI":"10.1002\/ijc.70772","type":"journal-article","created":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T05:34:53Z","timestamp":1791264893000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Systemic Inflammation Mediates the Association Between Plasma Epstein\u2013Barr Virus\n                    <scp>DNA<\/scp>\n                    and Mortality in Metastatic Nasopharyngeal Carcinoma"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-3328-2947","authenticated-orcid":false,"given":"Qin","family":"Liu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy Guangdong Provincial Clinical Research Center for Cancer, Sun Yat\u2010sen University Cancer Center  Guangzhou People's Republic of China"},{"name":"Department of Nasopharyngeal Cancer Sun Yat\u2010sen University Cancer Center  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi\u2010Ming","family":"Zeng","sequence":"additional","affiliation":[{"name":"Institute of Medical Technology, Peking University Health Science Center  Beijing China"},{"name":"Beijing Key Laboratory of Intelligent Neuromodulation and Brain Disorder Treatment  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu\u2010Wen","family":"Kuang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy Guangdong Provincial Clinical Research Center for Cancer, Sun Yat\u2010sen University Cancer Center  Guangzhou People's Republic of China"},{"name":"Department of Nasopharyngeal Cancer Sun Yat\u2010sen University Cancer Center  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu\u2010Chen","family":"Hua","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy Guangdong Provincial Clinical Research Center for Cancer, Sun Yat\u2010sen University Cancer Center  Guangzhou People's Republic of China"},{"name":"Department of Nasopharyngeal Cancer Sun Yat\u2010sen University Cancer Center  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-9492-8297","authenticated-orcid":false,"given":"Chuan\u2010Run","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy Guangdong Provincial Clinical Research Center for Cancer, Sun Yat\u2010sen University Cancer Center  Guangzhou People's Republic of China"},{"name":"Department of Nasopharyngeal Cancer Sun Yat\u2010sen University Cancer Center  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng\u2010Wen","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy Guangdong Provincial Clinical Research Center for Cancer, Sun Yat\u2010sen University Cancer Center  Guangzhou People's Republic of China"},{"name":"Department of Nasopharyngeal Cancer Sun Yat\u2010sen University Cancer Center  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Gong","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy Guangdong Provincial Clinical Research Center for Cancer, Sun Yat\u2010sen University Cancer Center  Guangzhou People's Republic of China"},{"name":"Department of Nasopharyngeal Cancer Sun Yat\u2010sen University Cancer Center  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia\u2010Yu","family":"Zhou","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy Guangdong Provincial Clinical Research Center for Cancer, Sun Yat\u2010sen University Cancer Center  Guangzhou People's Republic of China"},{"name":"Department of Nasopharyngeal Cancer Sun Yat\u2010sen University Cancer Center  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Deng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy Guangdong Provincial Clinical Research Center for Cancer, Sun Yat\u2010sen University Cancer Center  Guangzhou People's Republic of China"},{"name":"Department of Nasopharyngeal Cancer Sun Yat\u2010sen University Cancer Center  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia\u2010Huan","family":"Lu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy Guangdong Provincial Clinical Research Center for Cancer, Sun Yat\u2010sen University Cancer Center  Guangzhou People's Republic of China"},{"name":"Department of Nasopharyngeal Cancer Sun Yat\u2010sen University Cancer Center  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu\u2010Shu","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Nutrition Fuwai Shenzhen Hospital, Chinese Academy of Medical Sciences  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Guo","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy Guangdong Provincial Clinical Research Center for Cancer, Sun Yat\u2010sen University Cancer Center  Guangzhou People's Republic of China"},{"name":"Department of Nasopharyngeal Cancer Sun Yat\u2010sen University Cancer Center  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2828-5963","authenticated-orcid":false,"given":"Wei\u2010Xiong","family":"Xia","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy Guangdong Provincial Clinical Research Center for Cancer, Sun Yat\u2010sen University Cancer Center  Guangzhou People's Republic of China"},{"name":"Department of Nasopharyngeal Cancer Sun Yat\u2010sen University Cancer Center  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,5]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/S0140-6736(19)30956-0","article-title":"Nasopharyngeal Carcinoma","volume":"394","author":"Chen Y. 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American Journal of Roentgenology"},{"key":"e_1_2_13_27_1","doi-asserted-by":"crossref","first-page":"47004","DOI":"10.1289\/EHP5838","article-title":"A Quantile\u2010Based g\u2010Computation Approach to Addressing the Effects of Exposure Mixtures","volume":"128","author":"Keil A. P.","year":"2020","journal-title":"Environmental Health Perspectives"},{"key":"e_1_2_13_28_1","doi-asserted-by":"crossref","first-page":"2855","DOI":"10.1016\/j.mex.2019.11.008","article-title":"Repeated Holdout Validation for Weighted Quantile Sum Regression","volume":"6","author":"Tanner E. M.","year":"2019","journal-title":"MethodsX"},{"key":"e_1_2_13_29_1","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.oraloncology.2019.05.015","article-title":"Establishment and Validation of a Nomogram for Predicting Survival in Patients With de Novo Metastatic Nasopharyngeal Carcinoma","volume":"94","author":"Sun X. 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