目的:评估DNA甲基化测试的诊断效能,将该测试与单独的细胞学进行比较,单独的荧光原位杂交(FISH),细胞学加FISH,并探讨可能影响液体活检准确性的原因。
方法:我们在2019年4月至2022年5月期间纳入了37名患者和12名阴性对照者。所有患者均接受了根治性肾输尿管切除术,肾切除术,诊断性输尿管镜检查,或者组织活检.收集尿样进行DNA甲基化检测,细胞学,和鱼。计算了测试性能,绘制受试者工作特性曲线进行比较。
结果:患者年龄中位数为66岁,对于DNA甲基化测试和组织病理学,κ=0.576(P<.001)。敏感性,特异性,阳性预测值(PPV),DNA甲基化检测的阴性预测值(NPV)为76%,100%,100%,74%,分别,与31%相比,100%,100%,50%,分别,细胞学。敏感性,特异性,PPV,细胞学+FISH的NPV为66%,100%,100%,67%,分别。DNA甲基化检测曲线下面积(AUC)为0.879(P<.001),细胞学+FISH的AUC为0.828(P<.001)。
结论:DNA甲基化检测结果令人满意。用于检测上尿路尿路上皮癌的DNA甲基化测试显示出比单独细胞学或FISH细胞学更好的敏感性,但是组合测试的准确性仍然可以接受。需要对更大样本进行进一步的前瞻性研究,以证实这种有前途的方法的临床价值。
OBJECTIVE: To evaluate the diagnostic efficacy of a DNA methylation test, compare that test with cytology alone, fluorescence in situ hybridization (FISH) alone, and cytology plus FISH, and explore reasons that may influence the accuracy of liquid biopsy.
METHODS: We included 37 patients and 12 negative control individuals between April 2019 and May 2022. All patients had undergone radical nephroureterectomy, nephrectomy, diagnostic ureteroscopy, or tissue biopsy. Urine samples were collected for DNA methylation testing, cytology, and FISH. Test performance was calculated, and receiver operating characteristic curves were drawn for comparison.
RESULTS: Median patient age was 66 years, and κ = 0.576 (P < .001) for the DNA methylation test and tissue pathology. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the DNA methylation test were 76%, 100%, 100%, and 74%, respectively, compared with 31%, 100%, 100%, and 50%, respectively, for cytology. The sensitivity, specificity, PPV, and NPV of cytology plus FISH were 66%, 100%, 100%, and 67%, respectively. The area under the curve (AUC) of the DNA methylation test was 0.879 (P < .001), and the AUC of cytology plus FISH was 0.828 (P < .001).
CONCLUSIONS: The test performance of DNA methylation was satisfactory. The DNA methylation test for the detection of upper tract urothelial carcinoma demonstrated better sensitivity than did cytology alone or cytology with FISH, but the accuracy of the combined tests was still acceptable. Further prospective studies with larger samples are needed to confirm the clinical value of this promising method.