TY - JOUR
T1 - Hypermethylation of Sox17 gene is useful as a molecular diagnostic application in early gastric cancer
AU - Oishi, Yoshichika
AU - Watanabe, Yoshiyuki
AU - Yoshida, Yoshihito
AU - Sato, Yoshinori
AU - Hiraishi, Tetsuya
AU - Oikawa, Ritsuko
AU - Maehata, Tadateru
AU - Suzuki, Hiromu
AU - Toyota, Minoru
AU - Niwa, Hirohumi
AU - Suzuki, Michihiro
AU - Itoh, Fumio
PY - 2012/4
Y1 - 2012/4
N2 - 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.
AB - 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.
KW - DNA methylation
KW - Gastric cancer
KW - Gastric washes
KW - Sox17
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U2 - 10.1007/s13277-011-0278-y
DO - 10.1007/s13277-011-0278-y
M3 - Article
C2 - 22161215
AN - SCOPUS:84860273603
VL - 33
SP - 383
EP - 393
JO - Oncodevelopmental Biology and Medicine
JF - Oncodevelopmental Biology and Medicine
SN - 1010-4283
IS - 2
ER -
