CYP3A4 Gene Is a Novel Biomarker for Predicting a Poor Prognosis in Hepatocellular Carcinoma

CYP3A4 基因是预测肝细胞癌预后不良的新型生物标志物

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作者:Ryo Ashida, Yukiyasu Okamura, Keiichi Ohshima, Yuko Kakuda, Katsuhiko Uesaka, Teiichi Sugiura, Takaaki Ito, Yusuke Yamamoto, Takashi Sugino, Kenichi Urakami, Masatoshi Kusuhara, Ken Yamaguchi

Aim

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 operation at our Institution. The aim of this study was to identify novel genes displaying altered gene expression related to the survival and early recurrence after hepatectomy for hepatocellular carcinoma (HCC) using the

Conclusion

CYP3A4 was identified as a novel tumor suppressor gene related to a poor prognosis in HCC.

Methods

The present study included 92 patients. Genes with aberrant expression were selected by the difference of expression levels with ≥10-fold change between tumor and non-tumor tissues.

Results

GEP analysis showed that down-regulation was frequently observed in the PRSS8 (64%), CYP3A4 (61%) and EPCAM (57%) genes. Multivariate analysis revealed tumor stage ≥II (p=0.008) and down-regulation of the CYP3A4 gene (p=0.036) as independent predictor for overall survival. Furthermore, multivariate analysis identified maximum tumor diameter ≥74mm (p=0.008), presence of intrahepatic-metastasis (p=0.020), and down-regulation of CYP3A4 gene (p=0.019) as independent predictors for early recurrence.

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