TY - JOUR
T1 - CHD8 is an independent prognostic indicator that regulates Wnt/β-catenin signaling and the cell cycle in gastric cancer
AU - Sawada, Genta
AU - Ueo, Hiroki
AU - Matsumura, Tae
AU - Uchi, Ryutaro
AU - Ishibashi, Masahisa
AU - Mima, Kosuke
AU - Kurashige, Junji
AU - Takahashi, Yusuke
AU - Akiyoshi, Sayori
AU - Sudo, Tomoya
AU - Sugimachi, Keishi
AU - Doki, Yuichiro
AU - Mori, Masaki
AU - Mimori, Koshi
PY - 2013/9
Y1 - 2013/9
N2 - The chromodomain helicase DNA-binding (CHD) family comprises a class of chromatin remodeling enzymes. Previous studies suggest that CHD8 may negatively regulate various genes and signaling pathways, such as the Wnt/β-catenin pathway. However, few studies have investigated the role of CHD8 in cancer cells. We analyzed the expression of CHD8 in cancer lesions and corresponding non-cancerous tissues to demonstrate the prognostic significance of CHD8 expression in 101 cases of gastric cancer. We also investigated the functional implications of aberrant CHD8 expression by conducting gene set enrichment analysis (GSEA). Expression of CHD8 mRNA was significantly lower in gastric cancer tissues compared to that in corresponding normal tissues (P=0.003). In multivariate analysis for overall survival, we found that CHD8 expression was an independent prognostic factor in gastric cancer. Moreover, GSEA revealed that CHD8 was significantly associated with genes involved in the Wnt/β-catenin pathway and in the cell cycle. In addition, knockdown of CHD8 expression in the gastric cancer cell lines, MKN45 and NUGC4, promoted proliferation. In conclusion, the present study suggests that loss of CHD8 expression may be a novel indicator for biological aggressiveness in gastric cancer.
AB - The chromodomain helicase DNA-binding (CHD) family comprises a class of chromatin remodeling enzymes. Previous studies suggest that CHD8 may negatively regulate various genes and signaling pathways, such as the Wnt/β-catenin pathway. However, few studies have investigated the role of CHD8 in cancer cells. We analyzed the expression of CHD8 in cancer lesions and corresponding non-cancerous tissues to demonstrate the prognostic significance of CHD8 expression in 101 cases of gastric cancer. We also investigated the functional implications of aberrant CHD8 expression by conducting gene set enrichment analysis (GSEA). Expression of CHD8 mRNA was significantly lower in gastric cancer tissues compared to that in corresponding normal tissues (P=0.003). In multivariate analysis for overall survival, we found that CHD8 expression was an independent prognostic factor in gastric cancer. Moreover, GSEA revealed that CHD8 was significantly associated with genes involved in the Wnt/β-catenin pathway and in the cell cycle. In addition, knockdown of CHD8 expression in the gastric cancer cell lines, MKN45 and NUGC4, promoted proliferation. In conclusion, the present study suggests that loss of CHD8 expression may be a novel indicator for biological aggressiveness in gastric cancer.
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UR - http://www.scopus.com/inward/citedby.url?scp=84880641966&partnerID=8YFLogxK
U2 - 10.3892/or.2013.2597
DO - 10.3892/or.2013.2597
M3 - Article
C2 - 23835524
AN - SCOPUS:84880641966
SN - 1021-335X
VL - 30
SP - 1137
EP - 1142
JO - Oncology Reports
JF - Oncology Reports
IS - 3
ER -
