The down-regulation of the CYP2C19 gene is associated with aggressive tumor potential and the poorer recurrence-free survival of hepatocellular carcinoma
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Ryo Ashida1, Yukiyasu Okamura1, Keiichi Ohshima2, Yuko Kakuda3, Katsuhiko Uesaka1, Teiichi Sugiura1, Takaaki Ito1, Yusuke Yamamoto1, Takashi Sugino3, Kenichi Urakami4, Masatoshi Kusuhara5 and Ken Yamaguchi6
1Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Shizuoka, Japan
2Medical Genetics Division, Shizuoka Cancer Center Research Institute, Shizuoka, Japan
3Division of Pathology, Shizuoka Cancer Center, Shizuoka, Japan
4Cancer Diagnostics Research Division, Shizuoka Cancer Center Research Institute, Shizuoka, Japan
5Regional Resources Division, Shizuoka Cancer Center Research Institute, Shizuoka, Japan
6Shizuoka Cancer Center Hospital and Research Institute, Shizuoka, Japan
Yukiyasu Okamura, email: [email protected]
Keywords: hepatocellular carcinoma; integrated gene expression profiling; CYP2C19 gene; down-regulation; recurrence-free survival
Received: February 05, 2018 Accepted: April 05, 2018 Published: April 24, 2018
Project HOPE (High-tech Omics-based Patient Evaluation) began in 2014 using integrated gene expression profiling (GEP) of cancer tissues as well as diathesis of each patient who underwent an operation at our institution. The aim of this study was to clarify the association between the expression of cytochrome P450s (CYP) genes and recurrence of hepatocellular carcinoma (HCC). The present study included 92 patients. Genes with aberrant expression were selected based on a ≥10-fold difference in the expression between tumor and non-tumor tissues. The GEP analysis showed that the down-regulated genes in tumor tissue were CYP3A4 in 56 patients (61%), CYP2C8 in 44 patients (48%), CYP2C19 in 30 patients (33%), CYP2D6 in 11 patients (12%), CYP3A5 in 7 patients (8%) and CYP1B1 in 2 patients (2%). There was no patients with down-regulation of the CYP17A1 gene. A multivariate analysis revealed that the presence of microscopic portal invasion (hazard ratio [HR] 2.57, 95% confidence interval [CI] 1.30–5.05 P = 0.006), the presence of intrahepatic-metastasis (HR 3.09 95% CI 1.52–6.29 P = 0.002) and down-regulation of the CYP2C19 gene (HR 3.69 95% CI 1.83–7.46 P < 0.001) were independent predictors for the recurrence-free survival (RFS). The down-regulation of the CYP2C19 gene were correlated with the RFS in HCC.
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