CHD8 is an independent prognostic indicator that regulates Wnt/β-catenin signaling and the cell cycle in gastric cancer

Sawada,Genta; Ueo,Hiroki; Matsumura,Tae; Uchi,Ryutaro; Ishibashi,Masahisa; Mima,Kosuke; Kurashige,Junji; Takahashi,Yusuke; Akiyoshi,Sayori; Sudo,Tomoya; Sugimachi,Keishi; Doki,Yuichiro; Mori,Masaki; Mimori,Koshi

doi:10.3892/or.2013.2597

CHD8 is an independent prognostic indicator that regulates Wnt/β-catenin signaling and the cell cycle in gastric cancer

Authors:
- Genta Sawada
- Hiroki Ueo
- Tae Matsumura
- Ryutaro Uchi
- Masahisa Ishibashi
- Kosuke Mima
- Junji Kurashige
- Yusuke Takahashi
- Sayori Akiyoshi
- Tomoya Sudo
- Keishi Sugimachi
- Yuichiro Doki
- Masaki Mori
- Koshi Mimori
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Affiliations: Department of Surgery, Beppu Hospital, Kyushu University, Beppu 874-0838, Japan, Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita 565-0871, Japan
Published online on: July 8, 2013 https://doi.org/10.3892/or.2013.2597
Pages: 1137-1142

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Abstract

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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