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乙型肝炎病毒相关肝细胞癌关键生物标志物和信号通路的综合研究

Comprehensive investigation of key biomarkers and pathways in hepatitis B virus-related hepatocellular carcinoma.

作者信息

Liao Xiwen, Yu Tingdong, Yang Chengkun, Huang Ketuan, Wang Xiangkun, Han Chuangye, Huang Rui, Liu Xiaoguang, Yu Long, Zhu Guangzhi, Su Hao, Qin Wei, Deng Jianlong, Zeng Xianmin, Han Bowen, Han Quanfa, Liu Zhengqian, Zhou Xin, Liu Junqi, Gong Yizhen, Liu Zhengtao, Huang Jianlv, Lu Lei, Ye Xinping, Peng Tao

机构信息

Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Zhuang Autonomous Region, People's Republic of China.

Department of Hematology, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Zhuang Autonomous Region, People's Republic of China.

出版信息

J Cancer. 2019 Sep 7;10(23):5689-5704. doi: 10.7150/jca.31287. eCollection 2019.

Abstract

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. 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 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. 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 and 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 and also doing well in the prediction of HBV-related HCC prognosis. The diagnostic and prognostic values of and was confirmed in TCGA HCC patients. Key biomarkers and pathways identified in the present study may enhance the comprehend of the molecular mechanisms underlying hepatocarcinogenesis. Additionally, mRNA expression of and may serve as potential diagnostic and prognostic biomarkers for HBV-related HCC.

摘要

我们的研究旨在利用全基因组表达谱数据集和方法,探索乙型肝炎病毒(HBV)相关肝细胞癌(HCC)中的潜在关键生物标志物和信号通路。来自GSE14520的数据集用作训练队列,癌症基因组图谱数据集用作验证队列。通过该软件包进行差异表达基因(DEG)筛选。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、京都基因与基因组百科全书以及风险评分模型用于信号通路和基因鉴定。GSEA显示,几个信号通路和生物学过程与肝癌发生相关,如细胞周期、DNA修复和p53信号通路。共鉴定出160个DEG。DEG的富集功能和信号通路包括有毒物质分解和代谢过程,以及P450和p53信号通路。在WGCNA中,11个DEG被鉴定为核心DEG。在核心DEG的生存分析中,[此处原文缺失两个基因名称]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诊断中表现良好。由[此处原文缺失两个基因名称]组成的预后特征在预测HBV相关HCC预后方面也表现良好。[此处原文缺失两个基因名称]的诊断和预后价值在TCGA HCC患者中得到证实。本研究中鉴定出的关键生物标志物和信号通路可能会增强对肝癌发生潜在分子机制的理解。此外,[此处原文缺失两个基因名称]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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/601c/6843875/5a9d6a1d87e0/jcav10p5689g001.jpg

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