Abstract
BackgroundPromoter DNA methylation of Cysteine dioxygenase type1 (CDO1) gene has been clarified as a molecular diagnostic and prognostic indicator in various human cancers. The aim of this study is to investigate the clinical relevance of CDO1 methylation in primary biliary tract cancer (BTC).MethodsCDO1 DNA methylation was assessed by quantitative methylation-specific PCR in 108 BTC tumor tissues and 101 corresponding normal tissues. BTC was composed of extrahepatic cholangiocarcinoma (EHCC) (n = 81) and ampullary carcinoma (AC) (n = 27).ResultsThe CDO1 methylation value in the tumor tissues was significantly higher than that in the corresponding normal tissues (p<0.0001). The overall survival (OS) in EHCC patients with hypermethylation was poorer than those with hypomethylation (p = 0.0018), whereas there was no significant difference in AC patients. Multivariate analysis identified that CDO1 hypermethylation, preoperative serum CA19-9 and perineural invasion were independent prognostic factors in EHCC. The EHCC patients with CDO1 hypermethylation exhibited more dismal prognosis than those with hypomethylation even in low group of CA19-9 level (p = 0.0006).ConclusionsOur study provided evidence that promoter DNA methylation of CDO1 gene could be an excellent molecular diagnostic and prognostic biomarker in primary EHCC. The combination of CDO1 methylation and preoperative serum CA19-9 effectively enriched EHCC patients who showed the most dismal prognosis. These markers would be beneficial for clinical clarification of the optimal strategies in EHCC.
Highlights
Biliary tract cancer (BTC) is uncommon malignancy with an unfavorable prognosis
The aim of this study is to investigate the clinical relevance of Cysteine dioxygenase type1 (CDO1) methylation in primary biliary tract cancer (BTC)
The overall survival (OS) in Extrahepatic cholangiocarcinoma (EHCC) patients with hypermethylation was poorer than those with hypomethylation (p = 0.0018), whereas there was no significant difference in ampullary carcinoma (AC) patients
Summary
2017, BTC patients including gallbladder cancer were estimated as new cases of 11,740 and deaths of 3,830 in the United States.[1] Recent studies have reported that the global incidence has shown increasing tendency worldwide.[2,3] BTC is epithelial cancer that arise from biliary tree and can be classified by anatomic location. This classification differs from location but epidemiology, origin, treatment and prognosis. The aim of this study is to investigate the clinical relevance of CDO1 methylation in primary biliary tract cancer (BTC)
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