基于RNA测序数据的乙肝病毒相关早期肝细胞癌的诊断和预后

StephenW

Identification of diagnostic and prognostic biomarkers, and candidate targeted agents for hepatitis B virus-associated early stage hepatocellular carcinoma based on RNA-sequencing data
Zhili Zeng  1 , Zebiao Cao  2 , Ying Tang  1   3
Affiliations
Affiliations

    1
    Department of Oncology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510405, P.R. China.
    2
    Department of Endocrinology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510405, P.R. China.
    3
    Department of Oncology, Lingnan Medical Research Center of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510405, P.R. China.

    PMID: 32968453 PMCID: PMC7499982 DOI: 10.3892/ol.2020.12094

Abstract

Primary liver cancer is a rapidly progressing neoplasm with high morbidity and mortality rates. The present study aimed to identify potential diagnostic and prognostic biomarkers, and candidate targeted agents for hepatitis B virus (HBV)-associated early stage hepatocellular carcinoma (HCC). The gene expression profiles were extracted from the Gene Expression Omnibus database. Differentially expressed genes (DEGs), hub genes and the enrichment of signaling pathways were filtered out via a high-throughput sequencing method. The association between hub genes and the effects of the abnormal expression of hub genes on the rate of genetic variation, overall survival (OS), relapse-free survival (RFS), progression-free survival (PFS) and disease-free survival (DSS) of patients with HCC, as well as pathological stage and grade, were analyzed using different databases. A total of 1,582 DEGs were identified. Gene Ontology analysis revealed that the DEGs were mainly involved in the 'oxidation-reduction process', 'steroid metabolic process', 'metabolic process' and 'fatty acid beta-oxidation'. Enrichment analysis of Kyoto Encyclopedia of Genes and Genomes pathways revealed that the DEGs were mainly associated with 'metabolic pathways', 'PPAR signaling pathway', 'fatty acid degradation' and the 'cell cycle'. A total of 8 hub genes were extracted. Additionally, the abnormal expression levels of hub genes were closely associated with the OS, RFS, PFS and DSS of patients, the pathological stage and the grade. Furthermore, abnormal expression levels of the 8 hub genes were found in >30% of all samples. Several small molecular compounds that may reverse the altered DEGs were identified based on Connectivity Map analysis, including phenoxybenzamine, GW-8510, resveratrol, 0175029-0000 and daunorubicin. In conclusion, the dysfunction of fat metabolic pathways, the cell cycle, oxidation-reduction processes and viral carcinogenesis may serve critical roles in the occurrence of HBV-associated early stage HCC. The identified 8 hub genes may act as robust biomarkers for diagnosis and prognosis. Some small molecular compounds may be promising targeted agents against HBV-associated early stage HCC.

Keywords: DEGs; HBV; HCC; RNA-seq; hub genes; targeted agents.

Copyright: © Zeng et al.

StephenW

基于RNA测序数据的乙肝病毒相关早期肝细胞癌的诊断和预后生物标记物以及候选靶向药物的鉴定
曾志立1，曹彪标2，营堂1 3
隶属关系
隶属关系

    1个
    广州中医药大学附属广州中医药大学第一附属医院肿瘤科，广东广州510405
    2
    广州中医药大学附属广州中医药大学附属第一医院内分泌科，广东广州510405
    3
    广州中医药大学岭南医学研究中心肿瘤科，广东广州510405

    PMID：32968453 PMCID：PMC7499982 DOI：10.3892 / ol.2020.12094

抽象

原发性肝癌是一种快速发展的肿瘤，具有较高的发病率和死亡率。本研究旨在确定潜在的诊断和预后生物标志物，以及与乙肝病毒（HBV）相关的早期肝细胞癌（HCC）的候选靶向药物。从Gene Expression Omnibus数据库提取基因表达谱。差异表达基因（DEG），集线器基因和信号转导途径的富集通过高通量测序方法被滤除。集线器基因与集线器基因异常表达对遗传变异率，总生存率（OS），无复发生存率（RFS），无进展生存率（PFS）和无疾病生存率（DSS）之间的关联使用不同的数据库分析了HCC患者的）以及病理分期和等级。总共确定了1,582个DEG。基因本体分析表明，DEGs主要参与“氧化还原过程”，“类固醇代谢过程”，“代谢过程”和“脂肪酸β-氧化过程”。京都基因和基因组百科全书途径的富集分析表明，DEGs主要与“代谢途径”，“ PPAR信号传导途径”，“脂肪酸降解”和“细胞周期”有关。总共提取了8个中枢基因。此外，中枢基因的异常表达水平与患者的OS，RFS，PFS和DSS，病理分期和等级密切相关。此外，在所有样本中，> 30％的样本中发现了8个中枢基因的异常表达水平。根据连通性图分析，鉴定了可能逆转DEG改变的几种小分子化合物，包括苯氧基苯扎明，GW-8510，白藜芦醇，0175029-0000和柔红霉素。总之，脂肪代谢途径的功能障碍，细胞周期，氧化还原过程和病毒致癌作用可能在HBV相关的早期HCC发生中起关键作用。鉴定出的8个中枢基因可作为诊断和预后的可靠生物标志物。一些小分子化合物可能有望成为针对HBV相关早期HCC的靶向药物。

关键字：DEGs；乙肝病毒HCC； RNA序列中心基因目标代理商。

版权：©Zeng等。