Hypermethylation of Sox17 gene is useful as a molecular diagnostic application in early gastric cancer

Yoshichika Oishi, Yoshiyuki Watanabe, Yoshihito Yoshida, Yoshinori Sato, Tetsuya Hiraishi, Ritsuko Oikawa, Tadateru Maehata, Hiromu Suzuki, Minoru Toyota, Hirohumi Niwa, Michihiro Suzuki, Fumio Itoh

Research output: Contribution to journalArticle

29 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)383-393
Number of pages11
JournalTumor Biology
Volume33
Issue number2
DOIs
Publication statusPublished - 2012 Apr
Externally publishedYes

Fingerprint

Molecular Pathology
Stomach Neoplasms
DNA Methylation
Stomach
Genes
decitabine
Therapeutics
Recurrence
CpG Islands
Methyltransferases
Microarray Analysis
Methylation
Disease Progression
Neoplasms
Carcinogenesis
Genome
Gene Expression

Keywords

  • DNA methylation
  • Gastric cancer
  • Gastric washes
  • Sox17

ASJC Scopus subject areas

  • Cancer Research
  • Medicine(all)

Cite this

Oishi, Y., Watanabe, Y., Yoshida, Y., Sato, Y., Hiraishi, T., Oikawa, R., ... Itoh, F. (2012). Hypermethylation of Sox17 gene is useful as a molecular diagnostic application in early gastric cancer. Tumor Biology, 33(2), 383-393. https://doi.org/10.1007/s13277-011-0278-y

Hypermethylation of Sox17 gene is useful as a molecular diagnostic application in early gastric cancer. / Oishi, Yoshichika; Watanabe, Yoshiyuki; Yoshida, Yoshihito; Sato, Yoshinori; Hiraishi, Tetsuya; Oikawa, Ritsuko; Maehata, Tadateru; Suzuki, Hiromu; Toyota, Minoru; Niwa, Hirohumi; Suzuki, Michihiro; Itoh, Fumio.

In: Tumor Biology, Vol. 33, No. 2, 04.2012, p. 383-393.

Research output: Contribution to journalArticle

Oishi, Y, Watanabe, Y, Yoshida, Y, Sato, Y, Hiraishi, T, Oikawa, R, Maehata, T, Suzuki, H, Toyota, M, Niwa, H, Suzuki, M & Itoh, F 2012, 'Hypermethylation of Sox17 gene is useful as a molecular diagnostic application in early gastric cancer', Tumor Biology, vol. 33, no. 2, pp. 383-393. https://doi.org/10.1007/s13277-011-0278-y
Oishi, Yoshichika ; Watanabe, Yoshiyuki ; Yoshida, Yoshihito ; Sato, Yoshinori ; Hiraishi, Tetsuya ; Oikawa, Ritsuko ; Maehata, Tadateru ; Suzuki, Hiromu ; Toyota, Minoru ; Niwa, Hirohumi ; Suzuki, Michihiro ; Itoh, Fumio. / Hypermethylation of Sox17 gene is useful as a molecular diagnostic application in early gastric cancer. In: Tumor Biology. 2012 ; Vol. 33, No. 2. pp. 383-393.
@article{8304d9b254514e438c416dc208691f01,
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.",
keywords = "DNA methylation, Gastric cancer, Gastric washes, Sox17",
author = "Yoshichika Oishi and Yoshiyuki Watanabe and Yoshihito Yoshida and Yoshinori Sato and Tetsuya Hiraishi and Ritsuko Oikawa and Tadateru Maehata and Hiromu Suzuki and Minoru Toyota and Hirohumi Niwa and Michihiro Suzuki and Fumio Itoh",
year = "2012",
month = "4",
doi = "10.1007/s13277-011-0278-y",
language = "English",
volume = "33",
pages = "383--393",
journal = "Tumor Biology",
issn = "1010-4283",
publisher = "Springer Netherlands",
number = "2",

}

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

UR - http://www.scopus.com/inward/record.url?scp=84860273603&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84860273603&partnerID=8YFLogxK

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 - Tumor Biology

JF - Tumor Biology

SN - 1010-4283

IS - 2

ER -