Genome-wide screening of DNA methylation associated with lymph node metastasis in esophageal squamous cell carcinoma
| Autor: | Hidekazu Hiramoto, Ken Ichi Kozaki, Tatsuyuki Kawano, Tomoki Muramatsu, Eigo Otsuji, Daisuke Ichikawa, Satoru Miyano, Seiya Imoto, Naoto Fujiwara, Kousuke Tanimoto, Johji Inazawa, Hiroaki Nagata |
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| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine Pathology medicine.medical_specialty Esophageal Neoplasms pyrosequencing analysis Genomics Genome Epigenesis Genetic Cohort Studies 03 medical and health sciences 0302 clinical medicine medicine Humans predictive biomarker neoplasms Gene Aged Aged 80 and over DNA methylation lymph node metastasis business.industry Middle Aged digestive system diseases esophageal squamous cell carcinoma 030104 developmental biology Differentially methylated regions Oncology CpG site Lymphatic Metastasis 030220 oncology & carcinogenesis Carcinoma Squamous Cell Cancer research Biomarker (medicine) Pyrosequencing Female business Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.17147 |
| Popis: | Lymph node metastasis (LNM) of esophageal squamous cell carcinoma (ESCC) is well-known to be an early event associated with poor prognosis in patients with ESCC. Recently, tumor-specific aberrant DNA methylation of CpG islands around the promoter regions of tumor-related genes has been investigated as a possible biomarker for use in early diagnosis and prediction of prognosis. However, there are few DNA methylation markers able to predict the presence of LNM in ESCC. To identify DNA methylation markers associated with LNM of ESCC, we performed a genome-wide screening of DNA methylation status in a discovery cohort of 67 primary ESCC tissues and their paired normal esophageal tissues using the Illumina Infinium HumanMethylation450 BeadChip. In this screening, we focused on differentially methylated regions (DMRs) that were associated with LNM of ESCC, as prime candidates for DNA methylation markers. We extracted three genes, HOXB2, SLC15A3, and SEPT9, as candidates predicting LNM of ESCC, using pyrosequencing and several statistical analyses in the discovery cohort. We confirmed that HOXB2 and SEPT9 were highly methylated in LNM-positive tumors in 59 ESCC validation samples. These results suggested that HOXB2 and SEPT9 may be useful epigenetic biomarkers for the prediction of the presence of LNM in ESCC. |
| Databáze: | OpenAIRE |
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