caa a22 4500 445336013 CHVBK 20180317142755.0 cr unu---uuuuu 170323e20110401xx s 000 0 eng 10.1245/s10434-010-1393-5 doi (NATIONALLICENCE)springer-10.1245/s10434-010-1393-5 Identification and Validation of DNA Methylation Markers to Predict Lymph Node Metastasis of Esophageal Squamous Cell Carcinomas [Elektronische Daten] [Ken Gyobu, Satoshi Yamashita, Yasunori Matsuda, Hiroyasu Igaki, Tohru Niwa, Daiji Oka, Ryoji Kushima, Harushi Osugi, Shigeru Lee, Shigefumi Suehiro, Toshikazu Ushijima] Background: The presence of lymph node metastasis in esophageal squamous cell carcinoma (ESCC) patients is a critical factor for decision of treatment strategy. However, there have been no molecular markers to assess lymph node metastasis. In this study, we aimed to identify CpG islands (CGIs) whose DNA methylation statuses are associated with the presence of lymph node metastasis. Materials and Methods: A total of 96 ESCCs were divided into a screening set (n=48) and a validation set (n=48). Genome-wide methylation analysis was performed by methylated DNA immunoprecipitation-CGI microarray analysis. Methylation levels were analyzed by quantitative methylation-specific PCR (qMSP). Results: Genome-wide methylation analysis identified 25 CGIs differentially methylated between 8 ESCCs with lymph node metastasis and 4 without. In the screening set, 7 CGIs had significantly different methylation levels (P<0.05) between the ESCCs with and without lymph node metastasis, and cut-off methylation levels for these CGIs were determined. The validation set was analyzed with the prefixed cut-offs, and methylation statuses of 2 CGIs in the vicinities of PAX6 and ENST00000363328 were validated to be associated with the presence of lymph node metastasis. Using these 2 markers, the presence was predicted with a sensitivity of 93% and specificity of 57%. In addition, the methylation statuses of the 2 CGIs were significantly associated with disease-free survival (P=0.006). Conclusions: Methylation statuses of these 2 CGIs were significantly associated with the presence of lymph node metastasis of ESCCs. These CGIs are promising markers to predict the presence of lymph node metastases. Society of Surgical Oncology, 2010 Gyobu Ken Carcinogenesis Division, National Cancer Center Research Institute, Tokyo, Japan aut Yamashita Satoshi Carcinogenesis Division, National Cancer Center Research Institute, Tokyo, Japan aut Matsuda Yasunori Carcinogenesis Division, National Cancer Center Research Institute, Tokyo, Japan aut Igaki Hiroyasu Esophageal Surgery Division, National Cancer Center Hospital, Tokyo, Japan aut Niwa Tohru Carcinogenesis Division, National Cancer Center Research Institute, Tokyo, Japan aut Oka Daiji Carcinogenesis Division, National Cancer Center Research Institute, Tokyo, Japan aut Kushima Ryoji Pathology of Clinical Laboratory Division, National Cancer Center Hospital, Tokyo, Japan aut Osugi Harushi Department of Gastrointestinal Surgery, Graduate School of Medicine, Osaka City University, Osaka, Japan aut Lee Shigeru Department of Gastrointestinal Surgery, Graduate School of Medicine, Osaka City University, Osaka, Japan aut Suehiro Shigefumi Department of Cardiovascular Surgery, Graduate School of Medicine, Osaka City University, Osaka, Japan aut Ushijima Toshikazu Carcinogenesis Division, National Cancer Center Research Institute, Tokyo, Japan aut Annals of Surgical Oncology Springer-Verlag 18/4(2011-04-01), 1185-1194 1068-9265 18:4<1185 2011 18 10434 https://doi.org/10.1245/s10434-010-1393-5 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1245/s10434-010-1393-5 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Gyobu Ken Carcinogenesis Division, National Cancer Center Research Institute, Tokyo, Japan aut NATIONALLICENCE 700 1- Yamashita Satoshi Carcinogenesis Division, National Cancer Center Research Institute, Tokyo, Japan aut NATIONALLICENCE 700 1- Matsuda Yasunori Carcinogenesis Division, National Cancer Center Research Institute, Tokyo, Japan aut NATIONALLICENCE 700 1- Igaki Hiroyasu Esophageal Surgery Division, National Cancer Center Hospital, Tokyo, Japan aut NATIONALLICENCE 700 1- Niwa Tohru Carcinogenesis Division, National Cancer Center Research Institute, Tokyo, Japan aut NATIONALLICENCE 700 1- Oka Daiji Carcinogenesis Division, National Cancer Center Research Institute, Tokyo, Japan aut NATIONALLICENCE 700 1- Kushima Ryoji Pathology of Clinical Laboratory Division, National Cancer Center Hospital, Tokyo, Japan aut NATIONALLICENCE 700 1- Osugi Harushi Department of Gastrointestinal Surgery, Graduate School of Medicine, Osaka City University, Osaka, Japan aut NATIONALLICENCE 700 1- Lee Shigeru Department of Gastrointestinal Surgery, Graduate School of Medicine, Osaka City University, Osaka, Japan aut NATIONALLICENCE 700 1- Suehiro Shigefumi Department of Cardiovascular Surgery, Graduate School of Medicine, Osaka City University, Osaka, Japan aut NATIONALLICENCE 700 1- Ushijima Toshikazu Carcinogenesis Division, National Cancer Center Research Institute, Tokyo, Japan aut NATIONALLICENCE 773 0- Annals of Surgical Oncology Springer-Verlag 18/4(2011-04-01), 1185-1194 1068-9265 18:4<1185 2011 18 10434 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer