title: Hypermethylation of Sox17 gene is useful as a molecular diagnostic application in early gastric cancer.
abstract: Although minimal invasive treatment is widely accepted in the early stages of gastric cancer (GCa), we still do not have any appropriate risk markers to detect residual neoplasia and the potential for recurrence. We previously reported that aberrant DNA methylation is an early and frequent process in gastric carcinogenesis and could be useful for the detection of gastric neoplasia. Our goal is to find and identify some candidate genes, using genome-wide DNA methylation analysis, as a treatment marker for early gastric cancer (EGC). We performed methylated CpG island amplification microarray analysis using 12 gastric washes (six each of pre- and post-endoscopic treatment in each of the same patients). We finally focused on Sox17 gene. We examined the DNA methylation status of Sox17 in a validation set consisting of 128 wash samples (pre, 64; post, 64) at EGC. We next carried out functional studies to identify Sox17. Sox17 showed significant differential methylation between pre- and post-treatments in EGC patients (Sox17, p < 0.0001). Moreover, treating GCa cells that lacked Sox17 expression with a methyltransferase inhibitor, 5-aza-2'-deoxycytidine, restored the gene's expression. Additionally, the introduction of exogenous Sox17 into silenced cells suppressed colony formation. Gastric wash-based DNA methylation analysis could be useful for early detection of recurrence following endoscopic resection in EGC patients. Our data suggest that the silencing of Sox17 occurs frequently in EGC and may play a key role in the development and progression of the disease.
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, St. Marianna University School of Medicine, 2-16-1, Sugao, Miyamaeku, Kawasaki, Kanagawa, 216-8511, Japan.
authors.forename: Yoshichika
authors.initials: Y
authors.lastname: Oishi
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Yoshida
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Sato
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Hiraishi
authors.forename: Ritsuko
authors.initials: R
authors.lastname: Oikawa
authors.forename: Tadateru
authors.initials: T
authors.lastname: Maehata
authors.forename: Hiromu
authors.initials: H
authors.lastname: Suzuki
authors.forename: Minoru
authors.initials: M
authors.lastname: Toyota
authors.forename: Hirohumi
authors.initials: H
authors.lastname: Niwa
authors.forename: Michihiro
authors.initials: M
authors.lastname: Suzuki
authors.forename: Fumio
authors.initials: F
authors.lastname: Itoh
mesh_terms: D000368:Aged; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000235:genetics*; D045744:Cell Line, Tumor; D018899:CpG Islands; D019175:DNA Methylation; D000077209:Decitabine; D018450:Disease Progression; D055088:Early Detection of Cancer / Q000379:methods; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D012306:Risk; D055760:SOXF Transcription Factors / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C109188:SOX17 protein, human; D055760:SOXF Transcription Factors; D000077209:Decitabine; D001374:Azacitidine