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Abstract：
Traditional clinical modalities for diagnosing bladder urothelial carcinoma (BUC) remain limited due to their invasive nature, significant costs, discomfort associated with cystoscopy, and low sensitivity to urine cytology. Therefore, there is an urgent need to identify highly sensitive, specific, and noninvasive biomarkers for the early detection of this neoplasm. Hypermethylated TWIST1/Vimentin promoter may be a noninvasive biomarker using urine sample. We assessed the TWIST1/Vimentin promoter methylation status in urine samples using the Methylated Human TWIST1 and Vimentin Gene Detection Kit (Jiangsu MicroDiag Biomedicine Co., Ltd., China). The samples were collected from five groups: group 1 consisted of patients with BUC, group 2 contained other patients with urologic tumors, group 3 consisted of patients with benign diseases (e.g., urinary tract infections, lithiasis, and benign prostatic hyperplasia), Group 4 included UTUC (upper tract urothelial carcinoma) patients and group5 comprised healthy individuals. The study encompassed 77 BUC patients, and we evaluated the degree of methylation of the TWIST1/Vimentin gene in their urine samples. Notably, TWIST1/Vimentin positivity was significantly elevated in comparison to groups 2, 3 and 5 (all p < 0.001) at a rate of 77.9%, but no significant difference was observed when compared to group 4. In the relationship between TWIST1/Vimentin methylation and clinicopathological features of BC patients from our center, we found there was no significant association between TWIST1/Vimentin status and proteinuria and/or hematuria, and hypermethylation of TWIST1 / VIM genes was found in both high and low tumor grade and in both non-muscle invasive bladder cancer (stages Tis, Ta, or T1) and muscle-invasive bladder cancer (stage T2 or above). In the multivariable analysis for cancer detection, a positive TWIST1/Vimentin methylation were significantly linked to a heightened risk of BC. Moreover, TWIST1/Vimentin promoter methylation demonstrated an ability to detect BUC in urine samples with a sensitivity of 78% and a specificity of 83%. Our findings reveal that hypermethylation of the TWIST1/Vimentin promoter occurs in bladder urothelial carcinoma, and its high sensitivity and specificity suggest its potential as a screening and therapeutic biomarker for urothelial carcinoma of the bladder.
摘要：
诊断膀胱尿路上皮癌（BUC）的传统临床方法由于其侵袭性而受到限制。巨大的成本，与膀胱镜检查相关的不适，尿细胞学敏感性低.因此,迫切需要识别高度敏感，具体,和非侵入性生物标志物用于早期检测这种肿瘤。超甲基化的TWIST1/波形蛋白启动子可以是使用尿样的非侵入性生物标志物。我们使用甲基化的人TWIST1和波形蛋白基因检测试剂盒（江苏MicroDiag生物医学有限公司，Ltd.,中国）。样本来自五组：第1组由BUC患者组成，第2组包含其他泌尿系肿瘤患者，第3组由患有良性疾病的患者组成(例如，尿路感染,结石,和良性前列腺增生)，第4组包括UTUC（上尿路上皮癌）患者，第5组包括健康个体。该研究包括77名BUC患者，我们评估了尿液样本中TWIST1/波形蛋白基因的甲基化程度。值得注意的是,与第2、3和5组相比，TWIST1/Vimentin阳性显着升高（所有p<0.001），率为77.9％，但与第4组相比无显著差异。在TWIST1/Vimentin甲基化与我们中心BC患者临床病理特征的关系中，我们发现TWIST1/波形蛋白状态与蛋白尿和/或血尿之间没有显著关联，TWIST1/VIM基因的高甲基化在高、低肿瘤级别和非肌肉浸润性膀胱癌中都被发现（Tis，Ta,或T1）和肌肉浸润性膀胱癌（T2期或以上）。在癌症检测的多变量分析中，TWIST1/Vimentin甲基化阳性与BC风险升高显著相关.此外，TWIST1/波形蛋白启动子甲基化显示出检测尿液样品中BUC的能力，灵敏度为78％，特异性为83％。我们的发现揭示了TWIST1/波形蛋白启动子的超甲基化发生在膀胱尿路上皮癌,其高灵敏度和特异性表明其作为膀胱尿路上皮癌的筛查和治疗生物标志物的潜力。
