Poli Giulia, Brancorsini Stefano, Cochetti Giovanni, Barillaro Francesco, Egidi Maria Giulia, Mearini Ettore
Department of Surgical and Biomedical Sciences, Institute of Urological, Andrological Surgery and Minimally Invasive Techniques, University of Perugia, Italy.
Department of Experimental Medicine-Section of Terni, University of Perugia, Italy.
Urol Oncol. 2015 Dec;33(12):505.e1-7. doi: 10.1016/j.urolonc.2015.07.012. Epub 2015 Aug 15.
Inflammation plays a crucial role in different stages of cancer development and has long been associated with various types of cancer. Strong associations between dysregulated inflammasome activity and human heritable and acquired inflammatory diseases highlight the importance of this pathway in the immune response. The inflammasome is a large complex of NOD-like receptors called NLRs and drives growth and progression of different tumors. The aim of the present study was the characterization of some NLR genes, NLRP3, NLRP4, NLRP9, and NAIP, in urine sediment of patients with bladder cancer. Cytokeratin 20 and survivin were used as confirmed markers of bladder cancer.
For this study, 3 groups of subjects were considered: patients harboring bladder cancer, subjects affected by bladder inflammation (CTR1), and healthy subjects (CTR0). Total RNA was extracted from urine sediments and resulting complementary DNA was used for amplification by real-time polymerase chain reaction. Results were stratified according to tumor stage, grade, and risk of progression and recurrence.
The expression of cytokeratin 20 was always significantly higher in patients with bladder cancer when compared with that in both the tumor-free groups. NLRP3, NLRP4, NLRP9, and NAIP were overexpressed in patients with BCa when compared with that in CTR0. Stratification according to tumor stage, grade, and risk of recurrence and progression showed NLRP up-regulations in patients with early-stage cancer. NAIP was overexpressed in high-risk patients in comparison to CTR0 and in high-grade patients compared with CTR0 and CTR1.
These data are relevant to demonstrate the role of inflammasome in urothelial carcinoma, making NLR genes in urine sediment potential candidates for bladder cancer diagnosis.
炎症在癌症发展的不同阶段起着关键作用,长期以来一直与各种类型的癌症相关。炎性小体活性失调与人类遗传性和获得性炎症性疾病之间的强关联凸显了该通路在免疫反应中的重要性。炎性小体是一种由称为NLRs的NOD样受体组成的大型复合物,驱动不同肿瘤的生长和进展。本研究的目的是对膀胱癌患者尿沉渣中的一些NLR基因,即NLRP3、NLRP4、NLRP9和NAIP进行特征分析。细胞角蛋白20和生存素被用作膀胱癌的确诊标志物。
本研究纳入了3组受试者:患有膀胱癌的患者、受膀胱炎症影响的受试者(CTR1)和健康受试者(CTR0)。从尿沉渣中提取总RNA,并将得到的互补DNA用于实时聚合酶链反应扩增。结果根据肿瘤分期、分级以及进展和复发风险进行分层。
与两个无肿瘤组相比,膀胱癌患者中细胞角蛋白20的表达始终显著更高。与CTR0相比,膀胱癌患者中NLRP3、NLRP4、NLRP9和NAIP均过表达。根据肿瘤分期、分级以及复发和进展风险进行分层显示,早期癌症患者中NLRP上调。与CTR0相比,高危患者中NAIP过表达,与CTR0和CTR1相比,高级别患者中NAIP过表达。
这些数据证明了炎性小体在尿路上皮癌中的作用,使尿沉渣中的NLR基因成为膀胱癌诊断的潜在候选指标。