| 李晓宇,楼丽姝,张毅敏.尿液DNA甲基化检测在膀胱癌诊断中的应用：NEXT-BC研究解读[J].肿瘤学杂志,2025,31(10):913-921. |
| 尿液DNA甲基化检测在膀胱癌诊断中的应用：NEXT-BC研究解读 |
| Urinary DNA Methylation Test for Bladder Cancer Diagnosis： Interpretation of the NEXT-BC Study |
| 投稿时间：2025-06-16 |
| DOI：10.11735/j.issn.1671-170X.2025.10.B013 |
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| 中文关键词: 膀胱肿瘤 尿液DNA甲基化 PENK基因 诊断 灵敏度 特异度 |
| 英文关键词:bladder neoplasms urinary DNA methylation PENK gene diagnosis sensitivity specificity |
| 基金项目: |
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| 摘要点击次数: 72 |
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| 中文摘要: |
| 摘 要：膀胱癌是全球高发恶性肿瘤，早期发现可显著降低肌层浸润性癌的根治性切除风险，并提高生存率，但现有诊断手段存在局限，如侵入性强、费用高昂、灵敏度低等。近年研究发现，膀胱癌的发生与DNA甲基化等表观遗传变化密切相关，其中尿液中PENK基因甲基化可特异性反映肿瘤进展，但此前研究多为单中心小样本，亟需大规模验证。因此，开展了此项多中心、单盲、前瞻性临床研究（NEXT-BC研究）——尿液DNA甲基化检测在膀胱癌中的诊断，以评估尿液PENK甲基化检测的效能，并比较其与核基质蛋白22（nuclear matrix protein 22，NMP22）检测或尿液细胞学检测的诊断效能。2022年3月11日至2024年5月30日，韩国10家中心共纳入40岁以上、因血尿症状计划在3个月内接受膀胱镜检查的患者1 099例，其中219例确诊膀胱癌（176例为高级别或浸润性癌）。尿液DNA甲基化检测对高级别或浸润性癌的灵敏度为89.2%［95%置信区间（confidence interval，CI）：84.6%~93.8%］，特异度为87.8%（95%CI： 85.6%~89.9%），阳性预测值为61.3%（95%CI： 55.4%~67.3%），阴性预测值高达97.6%（95%CI：96.6%~98.7%）；对总体膀胱癌的灵敏度和特异度分别为78.1%（95%CI： 72.6%~83.6%）和88.8%（95%CI：86.7%~90.8%）。与NMP22检测（51.5%）或尿液细胞学检测（39.7%）相比，尿液DNA甲基化检测对高级别或浸润性膀胱癌的灵敏度显著更高（P<0.001）。尿液DNA甲基化检测对高级别或浸润性膀胱癌的灵敏度优于现有检测方法，且特异度较高，其阴性预测值优异，但阳性预测值仍有提升空间。未来需进一步验证其在其他种族群体中的表现及对临床决策的影响。 |
| 英文摘要: |
| Abstract： Bladder cancer is a highly prevalent cancer globally， earlier detection could reduce muscleinvasive bladder cancer requiring radical cystectomy and metastasis， thus improving survival. However， there are limitations to existing diagnostic methods， such as invasiveness， high cost and low sensitivity. In recent years， bladder cancer has been found to be closely associated with epigenetic changes such as DNA methylation， in which the methylation of the PENK gene in urine specifically reflects tumor progression. Most of the previous studies have been conducted on small samples from a single center， so large-scale validation is urgently needed. Therefore， this multicenter， single-blind， prospective clinical study， urinary DNA methylation test for bladder cancer diagnosis， was conducted to evaluate the performance of the urinary PENK methylation test and compare its diagnostic accuracy with that of the nuclear matrix protein 22 (NMP22) test or urine cytology test. From 11 March 2022 to 30 May 2024， 1 099 patients aged 40 years old and above who were scheduled to undergo cystoscopy within 3 months for symptoms of hematuria were enrolled at 10 centers in Korea， of whom 219 and 176 participants had bladder cancer and high-grade or invasive bladder cancer， respectively. The urinary DNA methylation test had sensitivity and specificity for high-grade or invasive bladder cancer of 89.2% ［95%(confidence interval，CI)： 84.6%~93.8%］ and 87.8% (95%CI： 85.6%~89.9%)， respectively， the positive predictive value was 61.3% (95%CI： 55.4%~67.3%)， and the negative predictive value was 97.6% (95%CI： 96.6%~98.7%). Sensitivity and specificity for overall bladder cancer were 78.1% (95%CI： 72.6%~83.6%) and 88.8% (95%CI： 86.7%~90.8%)， respectively. In comparison with the NMP22 test or urine cytology test， the urinary DNA methylation test showed significantly superior sensitivity for high-grade or invasive bladder cancer(P<0.001). The sensitivity of urinary DNA methylation test for high-grade or invasive bladder cancer was superior to existing detection methods， and its specificity was high.While this test had an excellent negative predictive value， its positive predictive value was suboptimal. Further validation of its performance in other racial groups and its impact on clinical decision-making is needed in the future. |
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