CBX4 and NOX4 Expression Are Associated With Chemoradiotherapy Response and Overall Survival in Locally Advanced Cervical Squamous Cell Carcinoma.
- 1Department of Radiation Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
Abstract
Background
Tissue biomarkers may improve risk stratification in locally advanced cervical cancer before definitive concurrent chemoradiotherapy (CCRT). We evaluated pretreatment expression of chromobox 4 (CBX4), NADPH oxidase 4 (NOX4), specificity protein 1 (SP1), and copper transporter 1 (CTR1) in relation to CCRT response and overall survival.Methods
In this retrospective 1:1 matched case-control study, pretreatment biopsies from 40 patients with locally advanced cervical squamous cell carcinoma (20 CCRT-resistant, 20 CCRT-sensitive) were quantified by AI-assisted digital pathology using H-scores. A parsimonious CBX4 + NOX4 logistic model was evaluated by apparent ROC, leave-one-out cross-validation (LOOCV), repeated stratified 5-fold cross-validation, and bootstrap optimism correction. Overall survival analyses were exploratory.Results
CBX4 and NOX4 expression was lower in CCRT-resistant tumors (median H-score: CBX4, 40.47 vs. 79.62; NOX4, 7.00 vs. 53.93; both p < 0.001), whereas SP1 and CTR1 did not differ. Apparent AUCs were 0.840 for CBX4 and 0.843 for NOX4. The two-marker model had an apparent AUC of 0.903, LOOCV AUC 0.845, repeated 5-fold CV AUC 0.854 ± 0.022, and bootstrap-corrected AUC 0.883. High CBX4 and NOX4 expression was associated with better 5-year overall survival; in joint Cox models, hazard ratios per 1-SD increase were 0.31 (95% CI 0.13-0.74) for CBX4 and 0.48 (0.26-0.90) for NOX4. No histochemically detectable copper deposits were observed.Conclusions
Lower pretreatment CBX4 and NOX4 expression was associated with a CCRT-resistant phenotype and poorer overall survival in this small, response-enriched cohort. Internal resampling suggested discrimination, but same-dataset 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.
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BibTeX
@article{pang2026cbx4,
title = {{CBX4 and NOX4 Expression Are Associated With Chemoradiotherapy Response and Overall Survival in Locally Advanced Cervical Squamous Cell Carcinoma.}},
author = {Xianfang Pang and Xiyun Qin and Lilin Que and Weiye Li and Zixuan Yang and Weili Yi and Jiao Tang and Yong Zhang and Shanshan Ma and Linjiang Pan and Fang Wu},
journal = {Cancer medicine},
year = {2026},
month = oct,
doi = {10.1002/cam4.72402},
url = {https://europepmc.org/article/MED/42897395},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - CBX4 and NOX4 Expression Are Associated With Chemoradiotherapy Response and Overall Survival in Locally Advanced Cervical Squamous Cell Carcinoma.
AU - Xianfang Pang
AU - Xiyun Qin
AU - Lilin Que
AU - Weiye Li
AU - Zixuan Yang
AU - Weili Yi
AU - Jiao Tang
AU - Yong Zhang
AU - Shanshan Ma
AU - Linjiang Pan
AU - Fang Wu
PY - 2026
DA - 2026/10/01
JO - Cancer medicine
DO - 10.1002/cam4.72402
UR - https://europepmc.org/article/MED/42897395
AB - Background Tissue biomarkers may improve risk stratification in locally advanced cervical cancer before definitive concurrent chemoradiotherapy (CCRT). We evaluated pretreatment expression of chromobox 4 (CBX4), NADPH oxidase 4 (NOX4), specificity protein 1 (SP1), and copper transporter 1 (CTR1) in relation to CCRT response and overall survival.Methods In this retrospective 1:1 matched case-control study, pretreatment biopsies from 40 patients with locally advanced cervical squamous cell carcinoma (20 CCRT-resistant, 20 CCRT-sensitive) were quantified by AI-assisted digital pathology using H-scores. A parsimonious CBX4 + NOX4 logistic model was evaluated by apparent ROC, leave-one-out cross-validation (LOOCV), repeated stratified 5-fold cross-validation, and bootstrap optimism correction. Overall survival analyses were exploratory.Results CBX4 and NOX4 expression was lower in CCRT-resistant tumors (median H-score: CBX4, 40.47 vs. 79.62; NOX4, 7.00 vs. 53.93; both p < 0.001), whereas SP1 and CTR1 did not differ. Apparent AUCs were 0.840 for CBX4 and 0.843 for NOX4. The two-marker model had an apparent AUC of 0.903, LOOCV AUC 0.845, repeated 5-fold CV AUC 0.854 ± 0.022, and bootstrap-corrected AUC 0.883. High CBX4 and NOX4 expression was associated with better 5-year overall survival; in joint Cox models, hazard ratios per 1-SD increase were 0.31 (95% CI 0.13-0.74) for CBX4 and 0.48 (0.26-0.90) for NOX4. No histochemically detectable copper deposits were observed.Conclusions Lower pretreatment CBX4 and NOX4 expression was associated with a CCRT-resistant phenotype and poorer overall survival in this small, response-enriched cohort. Internal resampling suggested discrimination, but same-dataset 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.
SN - 2045-7634
ER -