Husek Petr, Pacovsky Jaroslav, Chmelarova Marcela, Podhola Miroslav, Brodak Milos
Department of Urology, Faculty of Medicine in Hradec Kralove, Charles University in Prague and University Hospital in Hradec Kralove, Czech Republic.
Institute of Clinical Biochemistry and Diagnostics, Faculty of Medicine in Hradec Kralove, Charles University in Prague and University Hospital in Hradec Kralove, Czech Republic.
Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2017 Jun;161(2):210-216. doi: 10.5507/bp.2017.008. Epub 2017 Mar 22.
Genetic and epigenetic alterations play an important role in urothelial cancer pathogenesis. Deeper understanding of these processes could help us achieve better diagnosis and management of this life-threatening disease. The aim of this research was to evaluate the methylation status of selected tumor suppressor genes for predicting BCG response in patients with high grade non-muscle-invasive bladder tumor (NMIBC).
We retrospectively evaluated 82 patients with high grade non-muscle-invasive bladder tumor (stage Ta, T1, CIS) who had undergone BCG instillation therapy. We compared epigenetic methylation status in BCG-responsive and BCG-failure groups. We used the MS-MLPA (Methylation-Specific Multiplex Ligation-Dependent Probe Amplification probe sets ME001 and ME004. The control group was 13 specimens of normal urotel (bladder tissue)).
Newly identified methylations in high grade NMIBC were found in MUS81a, NTRK1 and PCCA. The methylation status of CDKN2B (P=0.00312) and MUS81a (P=0.0191) is associated with clinical outcomes of BCG instillation therapy response. CDKN2B and MUS81a unmethylation was found in BCG failure patients.
The results show that the methylation status of selected tumor suppressor genes (TSGs) has the potential for predicting BCG response in patients with NMIBC high grade tumors. Tumor suppressor genes such as CDKN2b, MUS81a, PFM-1, MSH6 and THBS1 are very promising for future research.
基因和表观遗传改变在尿路上皮癌发病机制中起重要作用。对这些过程的深入了解有助于我们更好地诊断和管理这种危及生命的疾病。本研究的目的是评估选定肿瘤抑制基因的甲基化状态，以预测高级别非肌层浸润性膀胱肿瘤（NMIBC）患者对卡介苗（BCG）治疗的反应。
我们回顾性评估了82例接受卡介苗灌注治疗的高级别非肌层浸润性膀胱肿瘤（Ta期、T1期、原位癌）患者。我们比较了卡介苗反应组和卡介苗治疗失败组的表观遗传甲基化状态。我们使用了甲基化特异性多重连接依赖探针扩增（MS-MLPA）（甲基化特异性多重连接依赖探针扩增探针组ME001和ME004。对照组为13份正常尿路上皮（膀胱组织）标本）。
在高级别NMIBC中发现MUS81a、NTRK1和PCCA有新的甲基化。CDKN2B（P = 0.00312）和MUS81a（P = 0.0191）的甲基化状态与卡介苗灌注治疗反应的临床结果相关。在卡介苗治疗失败的患者中发现CDKN2B和MUS81a未甲基化。
结果表明，选定肿瘤抑制基因（TSGs）的甲基化状态有可能预测高级别NMIBC患者对卡介苗治疗的反应。CDKN2b、MUS81a、PFM-1、MSH6和THBS1等肿瘤抑制基因在未来研究中非常有前景。
