Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
Urology and Nephrology Research Center, Shahid Labbafinejad Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Clin Biochem. 2024 Oct;131-132:110808. doi: 10.1016/j.clinbiochem.2024.110808. Epub 2024 Jul 26.
Current diagnostic approaches for bladder cancer (BLCA) are often invasive or lack the required sensitivity and specificity. This underscores the need for an early non-invasive diagnostic test for BLCA. This work aimed to explore the potential of molecular markers in urine-exfoliated cells for the diagnosis of non-muscle-invasive bladder cancer (NMIBC).
Urine specimens (n = 140) were collected from NMIBC patients (n = 68) and control subjects (31 healthy volunteers and 41 non-cancer patients with common urological diseases [CUD]. Total RNA was extracted from the cells isolated from urine specimens. mRNA expression of selected genes: CDC20, KRT15, FOXM1, CXCR2, UPK1B, MDK, KRT20, and KRT17 was determined using RT-qPCR. The receiver operating characteristic (ROC) curve was then plotted to obtain the area under the curve (AUC), specificity, and sensitivity of the urinary mRNA markers.
The expression of CDC20, MDK, UPK1B, FOXM1, KRT17, and KRT20 was up-regulated in samples obtained from low- and high-grade pathological grades of NMIBC compared to that measured in healthy subjects. Notably, MDK and KRT17 mRNA levels in the low- and high-grade cases were substantially higher than in normal and CUD groups. The AUC of the KRT17 and MDK combination in diagnosing NMIBC was 0.92, surpassing that of single genes. The sensitivity and specificity of the KRT17 and MDK combination were 74% and 94%, respectively. In diagnosing low-grade from healthy and CUD groups, analysis of the KRT17 and MDK combination yielded AUCs of 0.94 and 0.95, respectively, with sensitivities of 85% and 97%, and specificities of 93% and 85%.
The findings of this study revealed that KRT17 and MDK together are potential urine-based biomarkers for early diagnosis of NMIBC.
目前膀胱癌（BLCA）的诊断方法往往具有侵入性，或缺乏所需的灵敏度和特异性。这凸显了对 BLCA 进行早期非侵入性诊断测试的必要性。本研究旨在探索尿液脱落细胞中的分子标志物在诊断非肌肉浸润性膀胱癌（NMIBC）中的潜力。
收集了 140 例 NMIBC 患者（68 例）和对照组（31 名健康志愿者和 41 名患有常见泌尿科疾病[CUD]的非癌症患者）的尿液标本。从尿液标本中分离的细胞中提取总 RNA。使用 RT-qPCR 测定选定基因（CDC20、KRT15、FOXM1、CXCR2、UPK1B、MDK、KRT20 和 KRT17）的 mRNA 表达。然后绘制受试者工作特征（ROC）曲线以获得尿 mRNA 标志物的曲线下面积（AUC）、特异性和灵敏度。
与健康受试者相比，低级别和高级别 NMIBC 病理分级的样本中，CDC20、MDK、UPK1B、FOXM1、KRT17 和 KRT20 的表达上调。值得注意的是，低级别和高级别病例中 MDK 和 KRT17 mRNA 水平明显高于正常和 CUD 组。KRT17 和 MDK 联合诊断 NMIBC 的 AUC 为 0.92，超过了单个基因。KRT17 和 MDK 联合诊断 NMIBC 的灵敏度和特异性分别为 74%和 94%。在诊断低级别与健康和 CUD 组时，KRT17 和 MDK 联合分析的 AUC 分别为 0.94 和 0.95，灵敏度分别为 85%和 97%，特异性分别为 93%和 85%。
本研究结果表明，KRT17 和 MDK 联合是诊断 NMIBC 的潜在尿液生物标志物。
