| 引用本文: | 施旭佳,尧晨光,熊诗雯,谭婷,胡康洪.TCGA数据挖掘鉴定CDKN2A作为[]肝细胞癌的生物标记物[J].生物信息学,2024,22(4):252-261. |
| SHI Xujia,YAO Chenguang,XIONG Shiwen,TAN Ting,HU Kanghong.TCGA data mining of CDKN2A as a biomarker for hepatocellular carcinoma[J].Chinese Journal of Bioinformatics,2024,22(4):252-261. |
|
| |
|
|
| 本文已被：浏览 26次 下载 12次 |
码上扫一扫！ |
|
|
| TCGA数据挖掘鉴定CDKN2A作为[]肝细胞癌的生物标记物 |
|
施旭佳,尧晨光,熊诗雯,谭婷,胡康洪
|
|
(湖北工业大学中德生物医学中心,教育部与国家外专局“细胞调控与分子药物学科111创新引智基地”,工业发酵省部共建协同创新中心,湖北省工业微生物重点实验室,武汉 430068)[HJ1.6mm]
|
|
| 摘要: |
| 肝细胞癌(Hepatocellular carcinoma,HCC)占所有原发性肝脏恶性肿瘤的75%,且在亚洲和非洲死亡率最高。目前HCC主要病因有慢性肝炎病毒感染(包括乙型肝炎病毒(Hepatitis B virus,HBV)感染和丙型肝炎病毒(Hepatitis C virus,HCV)感染),酒精肝及非酒精性脂肪肝肝炎,但HCC的发病机制仍不明晰。为探究HCC发生发展相关机制,本研究对TCGA数据库中的HCC转录组数据进行挖掘,将377例HCC组织样本按照是否存在HBV感染分为CHB_HCC组(慢性HBV感染,270例)和Not_CHB_HCC组(非HBV感染,107例)共二组,二组中共包含43例非HBV相关癌旁组织样本作为对照。分别提取上述两组样本中肝癌组织与癌旁组织全基因转录组信息,进行基因转录水平差异分析,得到两组差异基因。将两组差异基因取交集,得到共有差异基因,随后对共有差异基因进行富集分析、生存分析及蛋白互作网络分析,最终得到与肝癌发生发展相关性最大的包括CDKN2A,CCNB1和EPO在内的9个hub基因。其中,CDKN2A在临床HCC样本癌组织中mRNA和部分样本中蛋白质水平均明显高于癌旁组织,此结果与转录组测序数据一致。尽管如此,生物学实验结果却显示,CDKN2A的过表达显著抑制了HepG2细胞的体外增殖和迁移。因此,本研究推测CDKN2A的过表达调控机制可能导致其在癌症早期,病毒感染及免疫逃逸等阶段促进HCC的发生发展。同时,生物信息学数据挖掘与分析CDKN2A的过表达与生存期的显著相关性,提示了其可作为HCC预后相关生物标记分子的潜力,这为HCC的诊断、预后和靶向治疗提供了新思路。 |
| 关键词: 肝细胞癌 慢性肝炎 CDKN2A hub基因 生物标志物 |
| DOI：10.12113/202301001 |
| 分类号:Q279 |
| 文献标识码:A |
| 基金项目:湖北省自然科学基金重点项目(No.2014CFA075)；发酵工程教育部重点实验室开放基金项目(No.202209EF09). |
|
| TCGA data mining of CDKN2A as a biomarker for hepatocellular carcinoma |
|
SHI Xujia, YAO Chenguang, XIONG Shiwen, TAN Ting, HU Kanghong
|
|
(Sino-German Biomedical Center, National “111” Center for Cellular Regulation and Molecular Pharmaceutics, Cooperative Innovation Center of Industrial Fermentation (Ministry of Education & Hubei Province), Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei University of Technology, Wuhan 430068, China)
|
| Abstract: |
| Hepatocellular carcinoma (HCC), which accounts for 75% of all primary liver malignancies, has the highest mortality rate in Asia and Africa. Currently, the main causes of HCC are chronic hepatitis virus infection such as hepatitis B virus (HBV) infection and hepatitis C virus (HCV) infection, alcoholic liver and non-alcoholic fatty liver hepatitis. However, the pathogenetic process of HCC is still unclear. In order to investigate the mechanisms associated with the tumorigenesis and progression of HCC, this study mines the TCGA database for HCC transcriptomic data and performed differential analysis on the gene expression data of liver cancer tissue and adjacent non-tumorous tissue from the transcriptomic data of 377 hepatocellular carcinoma patients with chronic hepatitis B (CHB_HCC,270 cases) or with other non-viral causes (Not_CHB_HCC,107 cases). 43 cases of non-HBV related adjacent tissue samples are included in the two groups as controls. Whole gene transcriptome information of the liver cancer tissue and the paracancerous tissue in the two groups of samples is extracted respectively, and difference analysis of gene transcription level is performed to obtain two groups of differential genes (DEGs). The two sets of DEGs are intersected to obtain the overlapping genes for enrichment analysis, survival analysis and protein-protein interaction network analysis. Subsequently, nine hub genes including CDKN2A, CCNB1and EPO,are identified to be most relevant to the tumorignesis and development of HCC. The results of biological analysis suggest that CDKN2A mRNA levels in HCC samples and CDKN2Aprotein levels in some HCC samples are significantly higher than those in the adjacent tissues, which is consistent with the transcriptome sequencing data. However, CDKN2Aover-expression significantly inhibited the proliferation and migration of HepG2 cells in vitro. Therefore, this study speculats that the over-expression regulation mechanism of CDKN2Amay lead to its promotion of HCC occurrence in the early stage of cancer, development, viral infection and immune escape. Meanwhile, bioinformatics data mining and analysis of the significant correlation between CDKN2Aover-expression and survival suggest its potential as a prognostic biomarker molecule for HCC, providing a new idea for the diagnosis, prognosis and targeted therapy of HCC. |
| Key words: Hepatocellular carcinoma Chronic hepatitis CDKN2A Hub genes Biomarker |
|
|
|
|
