Hentschel Anouk E, van den Helder Rianne, van Trommel Nienke E, van Splunter Annina P, van Boerdonk Robert A A, van Gent Mignon D J M, Nieuwenhuijzen Jakko A, Steenbergen Renske D M
Amsterdam UMC, Vrije Universiteit Amsterdam, Pathology, Cancer Center Amsterdam, de Boelelaan 1118, 1182 DB Amsterdam, The Netherlands.
Amsterdam UMC, Vrije Universiteit Amsterdam, Urology, Cancer Center Amsterdam, de Boelelaan 1118, 1182 DB Amsterdam, The Netherlands.
Cancers (Basel). 2021 Jan 31;13(3):535. doi: 10.3390/cancers13030535.
In urogenital cancers, urine as a liquid biopsy for non-invasive cancer detection holds great promise for future clinical application. Their anatomical position allows for the local shedding of tumor DNA, but recent data indicate that tumor DNA in urine might also result from transrenal excretion. This study aims to assess the origin of tumor-associated DNA in the urine of 5 bladder and 25 cervical cancer patients. Besides natural voided urine, paired urine samples were collected in which contact with the local tumor was circumvented to bypass local shedding. The latter concerned nephrostomy urine in bladder cancer patients, and catheter urine in cervical cancer patients. Methylation levels of , and were determined using paired bladder tumor tissues and cervical scrapes as a reference. Urinary methylation levels were compared to natural voided urine of matched controls. To support methylation results, mutation analysis was performed in urine and tissue samples of bladder cancer patients. Increased methylation levels were not only found in natural voided urine from bladder and cervical cancer patients, but also in the corresponding nephrostomy and catheter urine. DNA mutations detected in bladder tumor tissues were also detectable in all paired natural voided urine as well as in a subset of nephrostomy urine. These results provide the first evidence that the suitability of urine as a liquid biopsy for urogenital cancers relies both on the local shedding of tumor cells and cell fragments, as well as the transrenal excretion of tumor DNA into the urine.
在泌尿生殖系统癌症中，尿液作为一种用于非侵入性癌症检测的液体活检样本，在未来临床应用中具有巨大潜力。它们的解剖位置使得肿瘤DNA能够在局部脱落，但最近的数据表明，尿液中的肿瘤DNA也可能源于经肾排泄。本研究旨在评估5例膀胱癌患者和25例宫颈癌患者尿液中肿瘤相关DNA的来源。除了自然排尿的尿液外，还收集了配对的尿液样本，其中避免了与局部肿瘤的接触，以绕过局部脱落。对于膀胱癌患者而言，后者指肾造瘘尿液；对于宫颈癌患者而言，指导尿管尿液。以配对的膀胱肿瘤组织和宫颈刮片作为参考，测定了、和的甲基化水平。将尿液甲基化水平与匹配对照的自然排尿尿液进行比较。为了支持甲基化结果，对膀胱癌患者的尿液和组织样本进行了突变分析。不仅在膀胱癌和宫颈癌患者的自然排尿尿液中发现甲基化水平升高，在相应的肾造瘘尿液和导尿管尿液中也发现了甲基化水平升高。在膀胱肿瘤组织中检测到的DNA突变，在所有配对的自然排尿尿液以及一部分肾造瘘尿液中也可检测到。这些结果首次证明，尿液作为泌尿生殖系统癌症液体活检样本的适用性，既依赖于肿瘤细胞和细胞碎片的局部脱落，也依赖于肿瘤DNA经肾排泄进入尿液。
