N Srivatsa, Ps Hari, P Rahul, Paul Lista, Veeraiyan Durgadevi, Narikot Ambili, Veldore Vidya, Tanwar Nishtha, Sreekanthreddy Peddagangannagari, Goswami Hitesh, Kumar Rekha V, Srinath B S, Korlimarla Aruna
Department of Uro Oncology, Sri Shankara Cancer Hospital and Research Center, Sri Shankara Cancer Foundation, Bangalore, India.
Department of Molecular Oncology, Sri Shankara National Center for Cancer Prevention and Research, Sri Shankara Cancer Foundation, Bangalore, India.
BMC Cancer. 2025 May 22;25(1):916. doi: 10.1186/s12885-025-14273-y.
Bladder cancer represents a heterogeneous disease with distinct clinical challenges. Non-muscle invasive bladder cancer (NMIBC) typically presents as indolent and slow-growing, yet a critical clinical challenge remains: identifying which patients will progress to muscle-invasive disease requiring radical interventions. Early detection of progression propensity is essential, as once muscle invasion occurs, the risk of distant metastasis increases substantially, and treatment shifts from conservative TURBT (Transurethral Resection of Bladder Tumor) to aggressive surgical interventions with significant morbidity. Current risk stratification methods fail to adequately predict this transition in approximately 30% of cases, highlighting the urgent need for more accurate prognostic tools.
This retrospective study aimed to develop and validate a transcriptomics-based mRNA score for predicting early NMIBC recurrence, comparing its performance against traditional risk stratification methods.
We analyzed mRNA expression profiles from primary retrospective NMIBC tumor specimens (n = 25) collected between [2018-2022]. Traditional risk stratification tools, including EORTC scoring, were applied alongside our novel mRNA-based risk score to evaluate predictive accuracy for recurrence.
The transcriptomics-based mRNA score demonstrated a median prediction accuracy of 90% across 10,000 resampling iterations for predicting early NMIBC recurrence, significantly outperforming traditional EORTC risk scores. Our comprehensive gene set identified 435 differentially expressed genes associated with recurrence. Kaplan-Meier analysis showed significantly different recurrence-free survival between high and low mRNA risk score groups (Bonferroni corrected p-value < 0.0001).
This retrospective analysis confirms that mRNA expression-based risk stratification provides superior predictive accuracy compared to conventional clinicopathologic risk tools. Implementation of this gene signature could potentially reduce over-investigation and improve surveillance cost-effectiveness after TURBT in patients with primary high-risk NMIBC. These findings may transform the clinical management paradigm by enabling more personalized follow-up protocols based on molecular risk assessment.
膀胱癌是一种具有不同临床挑战的异质性疾病。非肌层浸润性膀胱癌（NMIBC）通常表现为惰性且生长缓慢，但仍存在一个关键的临床挑战：识别哪些患者会进展为需要根治性干预的肌层浸润性疾病。早期检测进展倾向至关重要，因为一旦发生肌层浸润，远处转移的风险会大幅增加，治疗也会从保守的经尿道膀胱肿瘤切除术（TURBT）转向具有显著发病率的积极手术干预。目前的风险分层方法在约30%的病例中未能充分预测这种转变，凸显了对更准确预后工具的迫切需求。
本回顾性研究旨在开发并验证一种基于转录组学的mRNA评分，用于预测早期NMIBC复发，并将其性能与传统风险分层方法进行比较。
我们分析了2018年至2022年期间收集的原发性回顾性NMIBC肿瘤标本（n = 25）的mRNA表达谱。将包括欧洲癌症研究与治疗组织（EORTC）评分在内的传统风险分层工具与我们基于mRNA的新型风险评分一起应用，以评估复发的预测准确性。
基于转录组学的mRNA评分在10,000次重采样迭代中预测早期NMIBC复发的中位预测准确率为90%，显著优于传统的EORTC风险评分。我们的综合基因集鉴定出435个与复发相关的差异表达基因。Kaplan-Meier分析显示，高mRNA风险评分组和低mRNA风险评分组之间的无复发生存率存在显著差异（Bonferroni校正p值<0.0001）。
这项回顾性分析证实，与传统的临床病理风险工具相比，基于mRNA表达的风险分层具有更高的预测准确性。在原发性高危NMIBC患者中，实施这种基因特征可能会减少过度检查，并提高TURBT后的监测成本效益。这些发现可能会通过基于分子风险评估实现更个性化的随访方案来改变临床管理模式。
