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Gene expression signatures predict outcome in non-muscle-invasive bladder carcinoma: a multicenter validation study
Lars Dyrskjøt1, Karsten Zieger, Francisco X Real
1Molecular Diagnostic Laboratory, Department of Clinical Biochemistry, Aarhus University Hospital, Skejby, Denmark.
Summary
Molecular classifiers accurately predict non-muscle-invasive bladder cancer outcomes. Gene expression signatures validated in a multicenter study aid in diagnosing disease stage, carcinoma in situ (CIS), and predicting recurrence and progression, improving patient treatment guidance.
Area of Science:
- Oncology
- Molecular Biology
- Genomics
Background:
- Non-muscle-invasive bladder cancer (NMIBC) requires reliable markers for predicting clinical course.
- Current diagnostic methods lack sufficient predictive power for disease recurrence and progression.
Purpose of the Study:
- To validate gene expression signatures for molecular diagnosis of NMIBC stage and carcinoma in situ (CIS).
- To assess the utility of molecular classifiers in predicting disease recurrence and progression in NMIBC patients.
Main Methods:
- Tumor samples from 404 NMIBC patients across five European countries were analyzed using custom microarrays.
- Four previously reported gene expression signatures were validated.
- Molecular classifications were compared against pathologic diagnosis and clinical outcomes.
Main Results:
- A 52-gene classifier strongly correlated with pathologic stage (P < 0.001) and predicted disease progression in T(a)/T(1) tumors (P < 0.001).
- An 88-gene classifier significantly predicted progression-free survival (P < 0.001) and cancer-specific survival (P = 0.001), proving an independent prognostic factor.
- A 68-gene classifier showed high correlation with histopathologic CIS diagnosis (OR, 5.8; P < 0.001).
Conclusions:
- Multicenter validation confirms the clinical utility of molecular classifiers for predicting NMIBC patient outcomes.
- These molecular tools can enhance treatment guidance for patients with non-muscle-invasive bladder cancer.