Establishment of diagnostic criteria for upper urinary tract urothelial carcinoma based on genome-wide DNA methylation analysis.
Establishment of diagnostic criteria for upper urinary tract urothelial carcinoma based on genome-wide DNA methylation analysis.
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DOI：
10.1080/15592294.2020.1767374
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发表时间：
2020-12
期刊：
影响因子：
3.7
通讯作者：
Kanai Y
中科院分区：
文献类型：
--
作者：
Fujimoto M;Arai E;Tsumura K;Yotani T;Yamada Y;Takahashi Y;Maeshima AM;Fujimoto H;Yoshida T;Kanai Y
本研究的目的是建立一个基于全基因组DNA甲基化谱的上尿路上皮癌（UTUC）的微创、准确的诊断系统。使用Infinium HumanMethylation 450 BeadChip进行全基因组DNA甲基化筛选，并使用焦磷酸测序验证DNA甲基化定量。我们分析了26个正常对照尿路上皮组织样本（C）、62个样本的初始队列（31个来自UTUC患者的非癌性尿路上皮[N]样本和31个相应UTUC样本）、82个样本的验证队列（41个N样本和41个UTUC样本）和14个膀胱尿路上皮癌（布克）样本。在初始队列中，我们确定了2，448个CpG位点，显示C和UTUC以及N和UTUC之间的DNA甲基化水平存在显著差异，但C和N之间没有差异。在这些CpG位点中，10个位于CpG岛或其海岸和架子内，包括在基因组结构域中，其中DNA甲基化水平得到稳定控制，甚至可以将UTUC与布克区分开。在这10个CpG和邻近位点（总共37个诊断组）中区分UTUC和N的受试者工作特征曲线分析产生的曲线下面积值为0.959-1.000，灵敏度和特异性分别为86.6-100%和93.5- 100%。在验证队列中成功证实了诊断影响。我们的标准是有用的诊断UTUC，无论其临床病理特征。将我们的标准应用于排尿样本将最终允许UTUC的非侵入性DNA甲基化诊断。
The aim of this study was to develop a less invasive and accurate diagnostic system for upper urinary tract urothelial carcinoma (UTUC) based on genome-wide DNA methylation profiling. Genome-wide DNA methylation screening was performed using the Infinium HumanMethylation450 BeadChip, and DNA methylation quantification was verified using pyrosequencing. We analysed 26 samples of normal control urothelial tissue (C), an initial cohort of 62 samples (31 samples of non-cancerous urothelium [N] from UTUC patients and 31 samples of the corresponding UTUCs), a validation cohort of 82 samples (41 N and 41 UTUC samples), and 14 samples of urinary bladder urothelial carcinoma (BUC). In the initial cohort, we identified 2,448 CpG sites showing significant differences in DNA methylation levels between both C and UTUC and N and UTUC, but not showing differences between C and N. Among these CpG sites, 10 were located within CpG islands or their shores and shelves included in genomic domains where DNA methylation levels are stably controlled, allowing discrimination of UTUC even from BUC. Receiver operating characteristic curve analysis for discrimination of UTUC from N in these 10 CpG and neighbouring sites (37 diagnostic panels in total) yielded area under the curve values of 0.959–1.000, with a sensitivity and specificity of 86.6–100% and 93.5–100%, respectively. The diagnostic impact was successfully confirmed in the validation cohort. Our criteria were useful for diagnosis of UTUC, regardless of its clinicopathological features. Application of our criteria to voided urine samples will ultimately allow non-invasive DNA methylation diagnosis of UTUC.
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影响因子：
2.1
作者：
Akita, Hirotaka;Kikuchi, Eiji;Jinzaki, Masahiro
通讯作者：
Jinzaki, Masahiro
影响因子：
4.5
作者：
Messer, Jamie;Shariat, Shahrokh F.;Raman, Jay D.
通讯作者：
Raman, Jay D.
影响因子：
6.6
作者：
Nakagawa, T;Kanai, Y;Hirohashi, S
通讯作者：
Hirohashi, S
影响因子：
5.7
作者：
Nishiyama, Naotaka;Arai, Eri;Kanai, Yae
通讯作者：
Kanai, Yae
DOI：
10.1523/jneurosci.5237-08.2009
发表时间：
2009-04-01
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Ding Q;Chen H;Xie X;Libby RT;Tian N;Gan L
通讯作者：
Gan L