Francesca Belardinilli, Meo Michela DE, Giudice Francesco Del, Scornajenghi Carlo Maria, Gazzaniga Paola, Berardinis Ettore DE, Marino Luca, Magliocca Fabio Massimo, Inbeh Chung Benjamin, Łaszkiewicz Jan, Magri Valentina, Giannini Giuseppe, Nicolazzo Chiara
Department of Molecular Medicine, Sapienza University of Rome, Rome, 00161, Italy.
Department of Maternal-Child and Urological Sciences, Sapienza University of Rome, Rome, 00161, Italy.
Oncol Res. 2025 Feb 28;33(3):723-731. doi: 10.32604/or.2024.056282. eCollection 2025.
Intravesical Bacillus Calmette-Guérin (BCG) therapy is a gold standard for patients with high-risk non-muscle invasive bladder cancer (NMIBC). Although a long-lasting therapeutic response is observed in most patients, BCG failure occurs in 30%-50% of patients and a progression to muscle-invasive disease is found in 10%-15%. Therefore, predicting high-risk patients who might not benefit from BCG treatment is critical. The purpose of this study was to identify, whether the presence of specific oncogenic mutations might be indicative of BCG treatment response.
Nineteen high-grade NMIBC patients who received intravesical BCG were retrospectively enrolled and divided into "responders" and "non-responders" groups. Tissue samples from transurethral resection of bladder cancer were performed before starting therapy and were examined using a multigene sequencing panel.
Mutations in TP53, FGFR3, PIK3CA, KRAS, CTNNB1, ALK and DDR2 genes were detected. TP53 and FGFR3 were found to be the most frequently mutated genes in our cohort (31.6% and 26.3%, respectively), followed by PIK3CA (15.8%). In the BCG-responsive patient group, 90% of samples were found to have mutated genes, with almost 50% of them showing mutations in tyrosine kinase receptors and CTNNB1 genes. On the other hand, in the BCG-unresponsive group, we found mutations in 44.4% of samples, mainly in TP53 gene.
Our findings suggest that a Next-Generation Sequencing (NGS) multigene panel is useful in predicting BCG response in patients with NMIBC.
膀胱内灌注卡介苗（BCG）治疗是高危非肌层浸润性膀胱癌（NMIBC）患者的金标准。尽管大多数患者观察到持久的治疗反应，但30%-50%的患者会出现BCG治疗失败，10%-15%的患者会进展为肌层浸润性疾病。因此，预测可能无法从BCG治疗中获益的高危患者至关重要。本研究的目的是确定特定致癌突变的存在是否可能指示BCG治疗反应。
回顾性纳入19例接受膀胱内BCG灌注的高级别NMIBC患者，并分为“反应者”和“无反应者”组。在开始治疗前采集膀胱癌经尿道切除术的组织样本，并使用多基因测序面板进行检测。
检测到TP53、FGFR3、PIK3CA、KRAS、CTNNB1、ALK和DDR2基因的突变。发现TP53和FGFR3是我们队列中最常发生突变的基因（分别为31.6%和26.3%），其次是PIK3CA（15.8%）。在BCG反应性患者组中，90%的样本发现有基因突变，其中近50%在酪氨酸激酶受体和CTNNB1基因中显示突变。另一方面，在BCG无反应组中，我们在44.4%的样本中发现了突变，主要在TP53基因中。
我们的研究结果表明，下一代测序（NGS）多基因面板可用于预测NMIBC患者的BCG反应。
