N Engl J Med 1995,333(1):32–41.PubMedCrossRef Competing interests The authors declared that they find more have no competing interests. Authors’ contributions Z-SZ, Z-YY and Y-YW design the study, LL, Y-XW, and H-QT carried out the Realtime quantitative RT-PCR and immunohistochemistry, Y-SS drafted the manuscript. All authors read and approved the final manuscript.”
“Background Hepatocellular carcinoma (HCC) is currently the fifth most common malignancy worldwide [1], and its overall incidence is steadily rising. In spite of the therapeutic

options for HCC such as hepatic resection [2], radiofrequency ablation [3], transcatheter arterial chemoembolization [4], and sorafenib [5], the prognosis of patients with advanced HCC remains poor [6, 7]. Therefore, research to clarify the mechanisms of hepatocarcinogenesis is urgently required [8]. Gene expression microarray analysis has revealed many cancer-related genes in HCC [9]. This method enables the expression status of all genes to be investigated simultaneously [10]. Furthermore, single nucleotide polymorphism (SNP) arrays

have made it possible to detect copy number changes Alpelisib cell line as well as copy-neutral loss of heterozygosity (LOH) [11]. Recently we developed a double combination array analysis consisting of gene expression array and SNP array analysis, and reported a number of tumor suppressor genes in HCC [12–17]. In these studies, we hypothesized that DNA methylation of the promoter region of these genes downregulated gene expression, causing HCC progression. In addition to this double combination array analysis, we obtained further data from the same specimens using methylation array analysis to make this association of DNA methylation more conclusive. We named it triple combination array analysis; this method seems

to be an efficient procedure for the detection of tumor suppressor genes of HCC [18]. Doublecortin domain-containing 2 (DCDC2) is a candidate tumor suppressor gene detected by this triple combination array analysis. This gene ADAM7 encodes a member of the doublecortin family [19], and contains two doublecortin domains. The doublecortin domain has been demonstrated to bind tubulin and enhance microtubule polymerization [19, 20], and mutations in this gene have been Tozasertib clinical trial associated with dyslexia [21–24]. However, there are only a few reports of the relationship between DCDC2 and cancer [25]. In addition, no previous study has researched the role of DCDC2 in HCC. Although it had been considered that DCDC2 gene had an impotrtant role in neuroendocrine systems, the expression of the gene was reported in GeneCards relatively strongest in liver in whole human organs including brain. Therefore, we selected this gene for this study, because we predicted the gene might have some role in liver.