Comprehensive investigation of key biomarkers and pathways in hepatitis B virus-related hepatocellular carcinoma
Comprehensive investigation of key biomarkers and pathways in hepatitis B virus-related hepatocellular carcinoma
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乙型肝炎病毒相关肝细胞癌关键生物标志物和通路的综合研究
DOI：
10.7150/jca.31287
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发表时间：
2019-01-01
影响因子：
3.9
通讯作者：
Peng, Tao
中科院分区：
文献类型：
--
作者：
Liao, Xiwen;Yu, Tingdong;Peng, Tao
目的：我们的研究旨在利用全基因组表达谱数据集和方法探索B肝炎病毒（HBV）相关肝细胞癌（HCC）的潜在关键生物标志物和途径。方法：使用来自GSE 14520的数据集作为训练队列，使用癌症基因组图谱数据集作为验证队列。差异表达基因（DEG）的筛选通过limma软件包进行。基因集富集分析（GSEA），加权基因共表达网络分析（WGCNA），基因本体论，基因和基因组的京都百科全书，和风险评分模型用于途径和基因的鉴定。结果如下：GSEA揭示了多种途径和生物学过程与肝癌的发生有关，如细胞周期、DNA修复和p53途径。总共确定了160名DEG。DEG的功能和途径主要包括有毒物质的分解代谢过程、P450和p53途径。11名指定专家组被确定为国民账户工作组的中心指定专家组。在hub DEG的生存分析中，PRC1和TOP2A的高表达与HBV相关HCC的不良临床结局显著相关，并且在HBV相关HCC的诊断中表现出良好的性能。由PRC1和TOP2A组成的预后标志物在预测HBV相关HCC预后方面也表现良好。PRC1和TOP2A在TCGA HCC患者中的诊断和预后价值得到证实。结论：在本研究中发现的关键生物标志物和途径可能会增强对肝癌发生的分子机制的理解。此外，PRC1和TOP2A的mRNA表达可能作为HBV相关HCC的潜在诊断和预后生物标志物。
Objective: Our study is aim to explore potential key biomarkers and pathways in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) using genome-wide expression profile dataset and methods. Methods: Dataset from the GSE14520 is used as the training cohort and The Cancer Genome Atlas dataset as the validation cohort. Differentially expressed genes (DEGs) screening were performed by the limma package. Gene set enrichment analysis (GSEA), weighted gene co-expression network analysis (WGCNA), gene ontology, the Kyoto Encyclopedia of Genes and Genomes, and risk score model were used for pathway and genes identification. Results: GSEA revealed that several pathways and biological processes are associated with hepatocarcinogenesis, such as the cell cycle, DNA repair, and p53 pathway. A total of 160 DEGs were identified. The enriched functions and pathways of the DEGs included toxic substance decomposition and metabolism processes, and the P450 and p53 pathways. Eleven of the DEGs were identified as hub DEGs in the WGCNA. In survival analysis of hub DEGs, high expression of PRC1 and TOP2A were significantly associated with poor clinical outcome of HBV-related HCC, and shown a good performance in HBV-related HCC diagnosis. The prognostic signature consisting of PRC1 and TOP2A also doing well in the prediction of HBV-related HCC prognosis. The diagnostic and prognostic values of PRC1 and TOP2A was confirmed in TCGA HCC patients. Conclusions: Key biomarkers and pathways identified in the present study may enhance the comprehend of the molecular mechanisms underlying hepatocarcinogenesis. Additionally, mRNA expression of PRC1 and TOP2A may serve as potential diagnostic and prognostic biomarkers for HBV-related HCC.