Ashida Ryo, Okamura Yukiyasu, Ohshima Keiichi, Kakuda Yuko, Uesaka Katsuhiko, Sugiura Teiichi, Ito Takaaki, Yamamoto Yusuke, Sugino Takashi, Urakami Kenichi, Kusuhara Masatoshi, Yamaguchi Ken
Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Shizuoka, Japan.
Department of Surgery, Keio University School of Medicine, Tokyo, Japan.
Cancer Genomics Proteomics. 2017 Nov-Dec;14(6):445-453. doi: 10.21873/cgp.20054.
BACKGROUND/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 results of integrated GEP analysis.
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.
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.
CYP3A4 was identified as a novel tumor suppressor gene related to a poor prognosis in HCC.
背景/目的：希望工程（基于高科技组学的患者评估）于2014年启动，采用癌症组织的综合基因表达谱（GEP）以及在我们机构接受手术的每位患者的素质。本研究的目的是利用综合GEP分析结果，鉴定与肝细胞癌（HCC）肝切除术后生存和早期复发相关的基因表达改变的新基因。
本研究纳入92例患者。通过肿瘤组织与非肿瘤组织之间表达水平差异≥10倍变化来选择表达异常的基因。
GEP分析显示，PRSS8（64%）、CYP3A4（61%）和EPCAM（57%）基因经常出现下调。多变量分析显示肿瘤分期≥II（p=0.008）和CYP3A4基因下调（p=0.036）是总生存的独立预测因素。此外，多变量分析确定最大肿瘤直径≥74mm（p=0.008）、肝内转移的存在（p=0.020）和CYP3A4基因下调（p=0.019）是早期复发的独立预测因素。
CYP3A4被鉴定为与HCC预后不良相关的新肿瘤抑制基因。
