Diagnostic and prognostic values of the mRNA expression of excision repair cross-complementation enzymes in hepatitis B virus-related hepatocellular carcinoma.
Diagnostic and prognostic values of the mRNA expression of excision repair cross-complementation enzymes in hepatitis B virus-related hepatocellular carcinoma.
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DOI：
10.2147/cmar.s179043
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发表时间：
2018
影响因子：
3.3
通讯作者：
Xie ZC
中科院分区：
文献类型：
--
作者：
Yang L;Xu M;Cui CB;Wei PH;Wu SZ;Cen ZJ;Meng XX;Huang QG;Xie ZC
本研究旨在利用全基因组表达谱芯片系统研究切除修复交叉互补（ERCC）基因在B型肝炎病毒（HBV）相关肝细胞癌（HCC）诊断和预后中的价值。从GSE 14520获得全基因组表达谱芯片。采用受试者工作特征曲线、生存分析和列线图分析ERCC基因的诊断和预后价值。通过基因集富集分析和全基因组共表达分析对ERCC 8的潜在功能进行了研究。ROC曲线分析表明，ERCC 1、ERCC 2、ERCC 3、ERCC 4、ERCC 5和ERCC 8基因在HBV相关性肝癌组织和癌旁组织中存在异常表达（ROC曲线下面积为0.623 ~ 0.744）。生存分析表明，ERCC 8高表达与HBV相关HCC复发（校正P=0.021; HR=0.643; 95%CI =0.442-0.937）和死亡（校正P=0.049; HR=0.631; 95%CI =0.399-0.998）风险显著降低相关。然后，我们还开发了两个诺模图用于HBV相关HCC的个体化预后预测。GSEA提示ERCC 8的高表达可能参与了能量代谢的生物学过程。ERCC 8的全基因组共表达分析和功能评估表明，这些共表达基因在DNA损伤和修复的多个生物学过程中显著富集。本研究提示6个ERCC基因（ERCC 1、ERCC 2、ERCC 3、ERCC 4、ERCC 5和ERCC 8）在HBV相关性肝癌肿瘤和癌旁组织中表达异常，ERCC 8的mRNA表达可能作为HBV相关性肝癌预后的潜在生物标志物。
The current study aims at using the whole genome expression profile chips for systematically investigating the diagnostic and prognostic values of excision repair cross-complementation (ERCC) genes in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Whole genome expression profile chips were obtained from the GSE14520. The receiver-operating characteristic (ROC) curve, survival analysis, and nomogram were used to investigate the diagnostic and prognostic values of ERCC genes. Investigation of the potential function of ERCC8 was carried out by gene set enrichment analysis (GSEA) and genome-wide coexpression analysis. ROC analysis suggests that six ERCC genes (ERCC1, ERCC2, ERCC3, ERCC4, ERCC5, and ERCC8) were dysregulated and may have potential to distinguish between HBV-related HCC tumor and paracancerous tissues (area under the curve of ROC ranged from 0.623 to 0.744). Survival analysis demonstrated that high ERCC8 expression was associated with a significantly decreased risk of recurrence (adjusted P=0.021; HR=0.643; 95% CI=0.442–0.937) and death (adjusted P=0.049; HR=0.631; 95% CI=0.399–0.998) in HBV-related HCC. Then, we also developed two nomograms for the HBV-related HCC individualized prognosis predictions. GSEA suggests that the high expression of ERCC8 may have involvement in the energy metabolism biological processes. As the genome-wide coexpression analysis and functional assessment of ERCC8 suggest, those coexpressed genes were significantly enriched in multiple biological processes of DNA damage and repair. The present study indicates that six ERCC genes (ERCC1, ERCC2, ERCC3, ERCC4, ERCC5, and ERCC8) were dysregulated between HBV-related HCC tumor and paracancerous tissues and that the mRNA expression of ERCC8 may serve as a potential biomarker for the HBV-related HCC prognosis.