{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T02:39:15Z","timestamp":1792809555395,"version":"4.5.0"},"reference-count":31,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T00:00:00Z","timestamp":1792368000000},"content-version":"vor","delay-in-days":18,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Tissue biomarkers may improve risk stratification in locally advanced cervical cancer before definitive concurrent chemoradiotherapy (CCRT). We evaluated pretreatment expression of chromobox\u00a04 (CBX4), NADPH oxidase 4 (NOX4), specificity protein 1 (SP1), and copper transporter 1 (CTR1) in relation to CCRT response and overall survival.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this retrospective 1:1 matched case\u2013control study, pretreatment biopsies from 40 patients with locally advanced cervical squamous cell carcinoma (20 CCRT\u2010resistant, 20 CCRT\u2010sensitive) were quantified by AI\u2010assisted digital pathology using H\u2010scores. A parsimonious CBX4\u2009+\u2009NOX4 logistic model was evaluated by apparent ROC, leave\u2010one\u2010out cross\u2010validation (LOOCV), repeated stratified 5\u2010fold cross\u2010validation, and bootstrap optimism correction. Overall survival analyses were exploratory.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      CBX4 and NOX4 expression was lower in CCRT\u2010resistant tumors (median H\u2010score: CBX4, 40.47 vs. 79.62; NOX4, 7.00 vs. 53.93; both\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001), whereas SP1 and CTR1 did not differ. Apparent AUCs were 0.840 for CBX4 and 0.843 for NOX4. The two\u2010marker model had an apparent AUC of 0.903, LOOCV AUC 0.845, repeated 5\u2010fold CV AUC 0.854\u2009\u00b1\u20090.022, and bootstrap\u2010corrected AUC 0.883. High CBX4 and NOX4 expression was associated with better 5\u2010year overall survival; in joint Cox models, hazard ratios per 1\u2010SD increase were 0.31 (95% CI 0.13\u20130.74) for CBX4 and 0.48 (0.26\u20130.90) for NOX4. No histochemically detectable copper deposits were observed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Lower pretreatment CBX4 and NOX4 expression was associated with a CCRT\u2010resistant phenotype and poorer overall survival in this small, response\u2010enriched cohort. Internal resampling suggested discrimination, but same\u2010dataset marker selection may introduce residual optimism and does not establish generalizability. Independent validation in a consecutively recruited cohort is required before clinical application. No mechanisms involving DNA repair, ROS, or chemoradiotherapy sensitivity were established.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cam4.72402","type":"journal-article","created":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T03:01:55Z","timestamp":1792465315000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>CBX4<\/scp>\n                    and\n                    <scp>NOX4<\/scp>\n                    Expression Are Associated With Chemoradiotherapy Response and Overall Survival in Locally Advanced Cervical Squamous Cell Carcinoma"],"prefix":"10.1002","volume":"15","author":[{"given":"Xianfang","family":"Pang","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology The First Affiliated Hospital of Guangxi Medical University  Nanning 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