Diagnostic markers of urothelial cancer based on DNA methylation analysis

Yoshitomo Chihara, Yae Kanai, Hiroyuki Fujimoto, Kokichi Sugano, Kiyotaka Kawashima, Gangning Liang, Peter A. Jones, Kiyohide Fujimoto, Hiroki Kuniyasu, Yoshihiko Hirao

研究成果: Article査読

36 被引用数 (Scopus)

抄録

BACKGROUND: Early detection and risk assessment are crucial for treating urothelial cancer (UC), which is characterized by a high recurrence rate, and necessitates frequent and invasive monitoring. We aimed to establish diagnostic markers for UC based on DNA methylation.

METHODS: In this multi-center study, three independent sample sets were prepared. First, DNA methylation levels at CpG loci were measured in the training sets (tumor samples from 91 UC patients, corresponding normal-appearing tissue from these patients, and 12 normal tissues from age-matched bladder cancer-free patients) using the Illumina Golden Gate methylation assay to identify differentially methylated loci. Next, these methylated loci were validated by quantitative DNA methylation by pyrosequencing, using another cohort of tissue samples (Tissue validation set). Lastly, methylation of these markers was analyzed in the independent urine samples (Urine validation set). ROC analysis was performed to evaluate the diagnostic accuracy of these 12 selected markers.

RESULTS: Of the 1303 CpG sites, 158 were hyper ethylated and 356 were hypo ethylated in tumor tissues compared to normal tissues. In the panel analysis, 12 loci showed remarkable alterations between tumor and normal samples, with 94.3% sensitivity and 97.8% specificity. Similarly, corresponding normal tissue could be distinguished from normal tissues with 76.0% sensitivity and 100% specificity. Furthermore, the diagnostic accuracy for UC of these markers determined in urine samples was high, with 100% sensitivity and 100% specificity.

CONCLUSION: Based on these preliminary findings, diagnostic markers based on differential DNA methylation at specific loci can be useful for non-invasive and reliable detection of UC and epigenetic field defect.

本文言語English
論文番号275
ページ(範囲)275
ページ数1
ジャーナルBMC cancer
13
DOI
出版ステータスPublished - 2013
外部発表はい

ASJC Scopus subject areas

  • 遺伝学
  • 腫瘍学
  • 癌研究

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