What question did this study set out to answer?

The study aims to evaluate chromosomal instability in bladder tumors as a potential biomarker for predicting recurrence risk after surgery.

March 15, 2026Open Access

Chromosomal instability as a predictive biomarker for recurrence risk following transurethral resection of NMIBC

Key Points

The study aims to evaluate chromosomal instability in bladder tumors as a potential biomarker for predicting recurrence risk after surgery.
Retrospective cohort study involving 50 bladder cancer patients.
DNA extracted from formalin-fixed paraffin-embedded samples.
Low-coverage whole-genome sequencing performed to analyze chromosomal instability.
Time-dependent Receiver Operating Characteristic analysis conducted to evaluate predictive efficacy.
Survival analysis performed using Kaplan-Meier and Cox proportional hazards models.
Significant differences in copy number alterations between recurrent and non-recurrent bladder cancer patients.
High chromosomal instability associated with poorer prognosis and shorter recurrence-free survival.
Median RFS of 22 months for high-CIN patients versus unreached for low-CIN patients.
CIN identified as an independent predictor of recurrence with a hazard ratio of 5.22.

Abstract

Objective To investigate chromosomal instability (CIN) in tumor tissues from transurethral resection of bladder tumor (TURBT) and evaluate its feasibility as a molecular biomarker for prognostic stratification in non-muscle-invasive bladder cancer (NMIBC). Methods In this retrospective single-center cohort study, DNA was extracted from formalin-fixed paraffin-embedded (FFPE) samples of 50 BC patients using the Qiagen nucleic acid extraction kit. The recurrence defined in this study refers to cystoscopically visible recurrence confirmed by biopsy or surgical pathology. All patients underwent follow-up until January 2025 in strict accordance with the protocol established by the EAU guidelines for NMIBC. Low-coverage whole-genome sequencing (LC-WGS) was performed to analyze CIN in bladder tumors. Time-dependent Receiver Operating Characteristic (ROC) analysis was performed to evaluate the predictive efficacy of CIN values for post-TURBT outcomes. Survival analysis was conducted using the Kaplan-Meier method (log-rank test), and associations between variables and recurrence-free survival (RFS) were assessed via Cox proportional hazards models. Results Recurrent bladder cancer patients exhibited significant copy number alterations (CNAs) differences in 67 gene segments versus non-recurrent patients. Time-dependent ROC analysis demonstrates that CIN values exhibit good predictive performance between the 2nd and 5th years. High CIN was significantly associated with tumor recurrence, higher tumor grade, with high-CIN patients exhibiting poorer prognosis (median RFS: 22 months vs. unreached in the low-CIN group, p = 0.009). Multivariate analysis confirmed high CIN as an independent predictor of recurrence (HR = 5.22, 95% CI: 1.52-17.93, P = 0.009). Patients with single-chromosome copy number abnormalities also showed worse outcomes (median RFS: 16–23 months) compared to those without such abnormalities. No significant difference in RFS was detected between Ta and T1 stages (P = 0.577). Conclusion High CIN exhibits a correlation with bladder tumor recurrence, higher tumor grade. High CIN or the presence of specific chromosomal abnormalities are indicative of an adverse prognosis. CIN may serve as a prognostic biomarker for predicting recurrence following TURBT, particularly between the 2nd and 5th years post-surgery.

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