Bioinformatics analysis reveals novel core genes associated with nonalcoholic fatty liver disease and nonalcoholic steatohepatitis
Bioinformatics analysis reveals novel core genes associated with nonalcoholic fatty liver disease and nonalcoholic steatohepatitis
复制标题
DOI：
10.1016/j.gene.2020.144549
复制
发表时间：
2020-06-05
期刊：
影响因子：
3.5
通讯作者：
Mi, Man
中科院分区：
文献类型：
--
作者：
Feng, Gong;Li, Xue-Ping;Mi, Man
非酒精性脂肪肝病 (NAFLD) 是最常见的肝脏疾病，与多种肝脏疾病相关，从非酒精性脂肪肝 (NAFL) 到非酒精性脂肪性肝炎 (NASH)、肝硬化和肝细胞癌 (HCC)。 NASH预计将成为肝移植最常见的适应症，NASH相关肝癌的年发病率为每1000人年5.29例。由于NAFLD的流行以及NAFLD进展的机制尚不清楚，详细阐明NAFLD的潜在机制非常重要。 NASH主要是由NAFL发展而来，因此了解NAFL向NASH进展的机制也具有重要意义。从Gene Expression Omnibus数据库下载NAFLD和NASH的基因表达芯片数据，以识别NAFLD和正常对照之间的差异表达基因（DEG）（NAFLD称为DEG）、NASH和正常组织之间（NASH-Normal称为DEG）、NASH和NAFL组织之间（NASH-NAFL称为DEG）。对于 NAFLD 组的 DEG，通过研究交叉的形式来鉴定关键基因。然后通过基因本体论 (GO) 和京都基因和基因组百科全书 (KEGG) 通路富集分析来分析 DEG 对 NASH 的潜在功能。使用 STRING 数据库构建蛋白质-蛋白质相互作用网络（PPI）。共鉴定出 249 个 DEG 和一个 NAFLD 关键基因。对于NASH-Normal，鉴定出514个DEG和11个中心基因，其中三个与HCC的生存分析密切相关，并且可能与NASH向HCC的进展密切相关。鉴定出了 NASH-NAFL (AKR1B10) 的一个关键基因。这些基因似乎介导 NAFLD 的分子机制，并且可能是 NASH 存在的有前途的生物标志物。
Nonalcoholic fatty liver disease (NAFLD) is the most frequent liver disease and associated with a wide spectrum of hepatic disorders ranging from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH), cirrhosis, and hepatocellular carcinoma (HCC). NASH is projected to become the most common indication for liver transplantation, and the annual incidence rate of NASH-related HCC is 5.29 cases per 1000 person-years. Owing to the epidemics of NAFLD and the unclear mechanism of NAFLD progression, it is important to elucidate the underlying NAFLD mechanisms in detail. NASH is mainly caused by the development of NAFL Therefore, it is also of great significance to understand the mechanism of progression from NAFL to NASH. Gene expression chip data for NAFLD and NASH were downloaded from the Gene Expression Omnibus database to identify differentially expressed genes (DEGs) between NAFLD and normal controls (called DEGs for NAFLD), as well as between NASH and normal tissue (called DEGs for NASH-Normal), and between NASH and NAFL tissue (called DEGs for NASH-NAFL). For DEGs for the NAFLD group, key genes were identified by studying the form of intersection. Potential functions of DEGs for NASH were then analyzed by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. A protein-protein interaction network (PPI) was constructed using the STRING database. A total of 249 DEGs and one key gene for NAFLD were identified. For NASH-Normal, 514 DEGs and 11 hub genes were identified, three of which were closely related to the survival analysis of HCC, and potentially closely related to progression from NASH to HCC. One key gene for NASH-NAFL (AKR1B10) was identified. These genes appear to mediate the molecular mechanism underlying NAFLD and may be promising biomarkers for the presence of NASH.