To detect new cancer-related genes that enable prediction of the prognosis of patients who undergo hepatectomy for HCC, we developed a double combination array analysis consisting

of expression array and SNP array analysis, and have reported several genes associated with hepatocarcinogenesis [12–17]. HDAC inhibitor Our experiment proves that these genes were hypermethylated in HCC tumor tissues, resulting in decreased expression and poorer prognosis, and we realized the double combination array analysis was an efficient procedure to identify new cancer-related genes via an epigenetic mechanism. However, this procedure required validation in HCC specimens on the basis that the downregulation of these genes occurred by methylation of promoter

regions. To ensure the involvement of gene methylation, we developed Pritelivir mw a triple combination array analysis that consists of expression array, SNP array, and methylation array analysis, and reported a new tumor suppressor gene using this procedure [18]. In the current study, we identified DCDC2 as a candidate tumor suppressor gene in HCC using triple combination array analysis. The promoter region of this gene was hypermethylated in many cancer tissues but only in a few normal tissues. The expression of DCDC2 in tumor tissues was decreased in methylated cases (P = 0.048). The overall survival of the patients with DCDC2 methylation was significantly worse than those without methylation Metalloexopeptidase (P = 0.048). DCDC2 has been reported

as a gene related with dyslexia [21–24]. DCDC2 protein is considered to have important roles in neural migration and construction of microtubules [19–21]. Massinen et al. showed downregulation of DCDC2 expression enhanced Wnt signaling, which is important in neuronal development [35]. Moreover, it is known that aberrant activation of the Wnt pathway is associated with human malignancies, including HCC [36, 37]. Therefore, it could be hypothesized that methylation of DCDC2 downregulates the expression of its protein product to cause activation of the Wnt pathway and worsen the prognosis of HCC patients. To support this hypothesis, various studies investigated secreted frizzled-related protein 1 (SFRP1) in HCC [38–41], and Kaur P et al. indicated SFRP1 expression was downregulated by methylation resulting in activation of the Wnt pathway and contributing to increased HCC cell growth and proliferation [41]. Therefore, DCDC2 might play a role in HCC in similar way to SFRP1. One of the limitations of this method is that we can obtain array information from only one pair of resected specimens at a time. However, we identified DCDC2 by triple combination array analysis. Thus, we investigated this gene in 48 resected HCC specimens and proved the impact of methylation in cancer tissues. The relevance of DCDC2 in the tumorigenesis of HCC could Ralimetinib supplier Therefore be considered as universal.