title: CHD8 is an independent prognostic indicator that regulates Wnt/β-catenin signaling and the cell cycle in gastric cancer.
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.
authors.affiliation: Department of Surgery, Beppu Hospital, Kyushu University, Beppu 874-0838, Japan.
authors.forename: Genta
authors.initials: G
authors.lastname: Sawada
authors.forename: Hiroki
authors.initials: H
authors.lastname: Ueo
authors.forename: Tae
authors.initials: T
authors.lastname: Matsumura
authors.forename: Ryutaro
authors.initials: R
authors.lastname: Uchi
authors.forename: Masahisa
authors.initials: M
authors.lastname: Ishibashi
authors.forename: Kosuke
authors.initials: K
authors.lastname: Mima
authors.forename: Junji
authors.initials: J
authors.lastname: Kurashige
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Sayori
authors.initials: S
authors.lastname: Akiyoshi
authors.forename: Tomoya
authors.initials: T
authors.lastname: Sudo
authors.forename: Keishi
authors.initials: K
authors.lastname: Sugimachi
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Doki
authors.forename: Masaki
authors.initials: M
authors.lastname: Mori
authors.forename: Koshi
authors.initials: K
authors.lastname: Mimori
mesh_terms: D000368:Aged; D015820:Cadherins / Q000037:antagonists & inhibitors / Q000235:genetics*; D002453:Cell Cycle / Q000235:genetics*; D049109:Cell Proliferation; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D010534:Peritoneal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000556:secondary; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D051153:Wnt Proteins / Q000235:genetics*; D051176:beta Catenin / Q000235:genetics*
chemical_list: C112316:CDH8 protein, human; C495270:CTNNB1 protein, human; D015820:Cadherins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D051153:Wnt Proteins; D051176:beta Catenin