Section of Medical Affairs, Xiangyang No. 1 People's Hospital, Hubei University of Medicine, Xiangyang, Hubei 441000, P.R. China.
Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China.
Mol Med Rep. 2018 Apr;17(4):5619-5626. doi: 10.3892/mmr.2018.8555. Epub 2018 Feb 2.
In order to identify the potential pathogenesis of hepatocellular carcinoma (HCC) developing from cirrhosis, a microarray‑based transcriptome profile was analyzed. The GSE63898 expression profile was downloaded from the Gene Expression Omnibus database, which included data from 228 HCC tissue samples and 168 cirrhotic tissue samples. The Robust Multi‑array Average in the Affy package of R was used for raw data processing and Student's t‑test was used to screen differentially expressed genes (DEGs). An enrichment analysis was then conducted using the Database for Annotation, Visualization and Integrated Discovery online tool, and the protein‑protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes and Cytoscape. Furthermore, the MCODE plug‑in of Cytoscape was used to conduct a sub‑module analysis. A total of 634 DEGs were identified between HCC and cirrhosis, of which 165 were upregulated and 469 were downregulated. According to the cut‑off criteria, the PPI network was constructed and Jun proto‑oncogene, AP‑1 transcription factor subunit (degree, 39), Fos proto‑oncogene, AP‑1 transcription factor subunit (degree, 34) and v‑myc avian myelocytomatosis viral oncogene homolog (degree, 32) were identified as the hub nodes of the PPI network. Based on the sub‑module analysis, four specific modules were identified. In particular, module 1 was significantly enriched in the chemokine signaling pathway, and C‑X‑C motif chemokine ligand 12, C‑C motif chemokine receptor 7 (CCR7) and C‑C motif chemokine ligand 5 (CCL5) were three important proteins in this module. Module 4 was significantly enriched in chemical carcinogenesis, and cytochrome P450 family 2 subfamily E member 1, cytochrome P450 family 2 subfamily C member 9 (CYP2C9) and cytochrome P450 family 2 subfamily A member 6 (CYP2A6) were three important proteins in this module. In conclusion, the present study revealed that CCR7, CCL5, CYP2C9 and CYP2A6 are novel genes identified in the development of HCC; however, the actual functions of these genes require verification.
为了确定从肝硬化发展为肝细胞癌（HCC）的潜在发病机制，对基于微阵列的转录组谱进行了分析。从基因表达综合数据库中下载了 GSE63898 表达谱，其中包括 228 个 HCC 组织样本和 168 个肝硬化组织样本的数据。使用 R 中的 Affy 包中的 Robust Multi-array Average 对原始数据进行处理，使用 Student's t-检验筛选差异表达基因（DEGs）。然后使用在线数据库 for Annotation, Visualization and Integrated Discovery 进行富集分析，并使用 Search Tool for the Retrieval of Interacting Genes 和 Cytoscape 构建蛋白质-蛋白质相互作用（PPI）网络。此外，使用 Cytoscape 的 MCODE 插件进行子模块分析。在 HCC 和肝硬化之间鉴定出 634 个 DEGs，其中 165 个上调，469 个下调。根据截止标准构建 PPI 网络，鉴定出 Jun 原癌基因、AP-1 转录因子亚基（度，39）、Fos 原癌基因、AP-1 转录因子亚基（度，34）和 v-myc 禽髓细胞瘤病毒致癌基因同源物（度，32）为 PPI 网络的枢纽节点。基于子模块分析，鉴定出四个特定模块。特别是，模块 1 在趋化因子信号通路中显著富集，并且 C-X-C 基序趋化因子配体 12、C-C 基序趋化因子受体 7（CCR7）和 C-C 基序趋化因子配体 5（CCL5）是该模块中的三个重要蛋白质。模块 4 在化学致癌作用中显著富集，并且细胞色素 P450 家族 2 亚家族 E 成员 1、细胞色素 P450 家族 2 亚家族 C 成员 9（CYP2C9）和细胞色素 P450 家族 2 亚家族 A 成员 6（CYP2A6）是该模块中的三个重要蛋白质。总之，本研究表明，CCR7、CCL5、CYP2C9 和 CYP2A6 是在 HCC 发展过程中鉴定的新基因；然而，这些基因的实际功能需要验证。
