Department of Pathology, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, The Netherlands.
Department of Medical Oncology, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, The Netherlands.
Eur Urol Oncol. 2021 Apr;4(2):215-226. doi: 10.1016/j.euo.2019.07.011. Epub 2019 Aug 9.
The 5-yr survival of early-stage renal cell carcinoma (RCC) is approximately 93%, but once metastasised, the 5-yr survival plummets to 12%, indicating that early RCC detection is crucial to improvement in survival. DNA methylation biomarkers have been suggested to be of potential diagnostic value; however, their current state of clinical translation is unclear and a comprehensive overview is lacking.
To systematically review and summarise all literature regarding diagnostic DNA methylation biomarkers for RCC.
We performed a systematic literature review of PubMed, EMBASE, Medline, and Google Scholar up to January 2019, according to the Preferred Reporting Items for Systematic Review and Meta-Analysis of Diagnostic Test Accuracy Studies (PRISMA-DTA) guidelines. Included studies were scored according to the Standards for Reporting of Diagnostic Accuracy Studies (STARD) criteria. Forest plots were generated to summarise diagnostic performance of all biomarkers. Level of evidence (LoE) and potential risk of bias were determined for all included studies.
After selection, 19 articles reporting on 44 diagnostic DNA methylation biomarkers and 11 multimarker panels were included; however, only 15 biomarkers were independently validated. STARD scores varied from 4 to 13 out of 23 points, with a median of 10 points. Large variation in subgroups, methods, and primer locations was observed. None of the reported biomarkers exceeded LoE III, and the majority of studies reported inadequately.
None of the reported biomarkers exceeded LoE III, indicating their limited clinical utility. Moreover, study reproducibility and further development of these RCC biomarkers are greatly hampered by inadequate reporting.
In this report, we reviewed whether specific biomarkers could be used to diagnose the most common form of kidney cancer. We conclude that due to limited evidence and reporting inconsistencies, none of these biomarkers can be used in clinical practice, and further development towards clinical use is hindered.
早期肾细胞癌（RCC）的 5 年生存率约为 93%，但一旦转移，5 年生存率骤降至 12%，这表明早期 RCC 的检测对于提高生存率至关重要。DNA 甲基化生物标志物具有潜在的诊断价值，但目前其临床转化状态尚不清楚，也缺乏全面的概述。
系统回顾和总结所有关于 RCC 的诊断性 DNA 甲基化生物标志物的文献。
我们根据诊断准确性测试研究的系统评价和荟萃分析的首选报告项目（PRISMA-DTA）指南，对 PubMed、EMBASE、Medline 和 Google Scholar 进行了系统的文献回顾，截至 2019 年 1 月。纳入的研究根据诊断准确性研究的报告标准（STARD）标准进行评分。生成森林图以总结所有生物标志物的诊断性能。对所有纳入的研究确定了证据水平（LoE）和潜在偏倚风险。
经过筛选，有 19 篇文章报道了 44 种诊断性 DNA 甲基化生物标志物和 11 种多标志物组合，其中只有 15 种生物标志物是独立验证的。STARD 评分从 23 分中的 4 分到 13 分不等，中位数为 10 分。在亚组、方法和引物位置方面存在很大差异。报道的生物标志物中没有一个超过 LoE III，大多数研究报告不充分。
没有一个报道的生物标志物超过 LoE III，这表明它们的临床实用性有限。此外，由于报告不充分，这些 RCC 生物标志物的研究可重复性和进一步开发受到极大阻碍。
在本报告中，我们评估了特定的生物标志物是否可用于诊断最常见的肾癌。我们的结论是，由于证据有限且报告不一致，这些生物标志物目前都不能用于临床实践，且进一步开发以用于临床应用受到阻碍。
