{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T15:33:10Z","timestamp":1792683190891,"version":"4.5.0"},"reference-count":36,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,11,14]],"date-time":"2024-11-14T00:00:00Z","timestamp":1731542400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Carcinogenesis"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Cisplatin\u2010based chemotherapy is the recommended therapy for muscle\u2010invasive bladder cancer (MIBC). However, the efficacy of MIBC for chemotherapy is only about 40%. Therefore, predictors of therapy response are urgently needed. Neutrophils form neutrophil extracellular traps (NETs), a network structure, and growing evidence indicated that it could be a prognostic and predictive marker in cancer. In MIBC, the predictive role of NETs in chemotherapy resistance is unclear. We used the Least Absolute Shrinkage and Selection Operator (LASSO) logistic regression analyses to develop a NETs\u2010associated signature score (NETs\u2010score) for therapeutic response prediction in the discovery cohort (GSE169455). Then the NETs score\u2010based risk stratification was verified in two validation cohorts (Taber et al.'s cohort, our institutional cohort). In the training cohort, high NETs\u2010score was associated with poor chemotherapy response (AUC\u2009=\u20090.781) and reduced recurrence\u2010free survival (RFS) (hazard ratio [HR]\u2009=\u20092.07, 95% confidence interval [CI]: [1.26\u20133.40], <jats:italic>p<\/jats:italic>\u2009=\u20090.003) in MIBC patients. The NETs\u2010score was also demonstrated to be a predictive factor for the efficacy of neoadjuvant chemotherapy in the validation cohort (AUC\u2009=\u20090.731). The accuracy of the NETs\u2010score was superior to other chemotherapy response predictors such as Ba\/Sq expression subtype (AUC\u2009=\u20090.711), BRCA2 mutation (AUC\u2009=\u20090.692) and ERCC2 mutation (AUC\u2009=\u20090.548). Furthermore, in our center cohort, the expression level of H3Cit showed a significant difference between the response and no\u2010response group (<jats:italic>p<\/jats:italic>\u2009=\u20090.01). Through immunohistochemical validation, NETs was an independent predictor of MIBC neoadjuvant chemotherapy efficacy as determined by the multivariate logistic regression analysis (OR\u2009=\u20095.94, 95% CI: 1.20\u201345.50, <jats:italic>p<\/jats:italic>\u2009=\u20090.045). Patients with high levels of NETs predicted poor response to neoadjuvant chemotherapy. This study was the first to reveal the correlation between the level of NETs in MIBC and the efficacy of chemotherapy, which may provide a theoretical basis regarding NETs inhibitors.<\/jats:p>","DOI":"10.1002\/mc.23844","type":"journal-article","created":{"date-parts":[[2024,11,14]],"date-time":"2024-11-14T14:29:09Z","timestamp":1731594549000},"page":"305-316","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Predictive Value of Neutrophil Extracellular Traps in Neoadjuvant Chemotherapy for Muscle\u2010Invasive Bladder Cancer"],"prefix":"10.1002","volume":"64","author":[{"given":"Bingqing","family":"Shang","sequence":"first","affiliation":[{"name":"Department of Urology, National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China"},{"name":"Department of Breast Medical Oncology Zhejiang Cancer Hospital Hangzhou China"},{"name":"Hangzhou Institute of Medicine (HIM) Chinese Academy of Sciences Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhilong","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Urology Guiqian International General Hospital Guiyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruiyang","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Urology Peking University Third Hospital Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Wu","sequence":"additional","affiliation":[{"name":"Hangzhou Institute of Medicine (HIM) Chinese Academy of Sciences Hangzhou China"},{"name":"Department of Urology Zhejiang Cancer Hospital Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wang","family":"Qu","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3150-2751","authenticated-orcid":false,"given":"Wen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Immunology, National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aiping","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Feng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingang","family":"Bi","sequence":"additional","affiliation":[{"name":"Department of Urology, National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-6795-7040","authenticated-orcid":false,"given":"Jianzhong","family":"Shou","sequence":"additional","affiliation":[{"name":"Department of Urology, National Cancer Center\/National 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