天然产物研究与开发 ›› 2022, Vol. 34 ›› Issue (8): 1415-1429.doi: 10.16333/j.1001-6880.2022.8.016

• 数据研究 • 上一篇    下一篇

基于关键致病基因筛选的肝癌临床预后及中药靶向治疗的生物信息学研究

吴   佳1,2,吴嫚婷1,3,龙   荣1,2,仇婧玥1,3,喻   昶1,3,熊   萌1,3,曾梅艳3*,宋厚盼1,3*   

  1. 1湖南中医药大学中医诊断学湖南省重点实验室;2湖南中医药大学医学院;3湖南中医药大学中医学院,长沙 410208
  • 出版日期:2022-08-28 发布日期:2022-09-08
  • 基金资助:
    国家自然科学基金(81703920,82004427);湖湘青年科技创新人才项目(2021RC3101);湖南省教育厅科学研究重点项目(21A0240)

Bioinformatics study on clinical prognosis of liver cancer and targeted therapy of traditional Chinese medicine based on screening of core pathogenic genes

WU Jia1,2,WU Man-ting1,3,LONG Rong1,2,QIU Jing-yue1,3,YU Chang1,3,XIONG Meng1,3,ZENG Mei-yan3*,SONG Hou-pan1,3*
  

  1. 1Hunan Provincial Key Laboratory of Diagnostic Research in Chinese Medicine,Hunan University of Chinese Medicine;2Faculty of Medicine,Hunan University of Chinese Medicine;3Faculty of Traditional Chinese Medicine,Hunan University of Chinese Medicine,Changsha 410208,China
  • Online:2022-08-28 Published:2022-09-08

摘要:

通过生物信息学方法筛选肝癌关键致病基因,探究其表达水平、致病机制、免疫浸润、突变及预后情况,并进一步挖掘潜在的可用于肝癌靶向治疗的中药。通过数据集GSE19665分析正常和肝癌组织的差异表达基因(differentially expressed genes,DEGs);对DEGs进行GO和KEGG分析,构建DEGs蛋白互作网络并筛选肝癌发病关键基因;对关键基因进行突变、免疫浸润、表达及预后分析;挖掘潜在的治疗肝癌的中药和天然活性成分。筛选得到显著性DEGs 159个,主要涉及免疫、炎症反应,参与p53、mTOR等信号通路;筛选出10个关键基因,CDC20等四个基因在肝癌组织的表达显著升高,高表达组患者的总生存期明显降低;关键基因突变患者的总生存期和无病生存期均明显降低;关键基因表达与免疫细胞浸润密切相关;以关键基因为靶点筛选得到36种中药和105种中药活性成分。本研究鉴定出了肝癌关键致病基因,其异常表达与肝癌的不良预后、免疫细胞浸润密切相关,挖掘出潜在的治疗肝癌的中药及其活性成分,研究结果可为肝癌的诊断、治疗及预后提供科学依据。

关键词: 肝癌, 关键基因, 生物信息学, 临床预后, 免疫细胞浸润, 中药

Abstract:

The key pathogenic genes of liver cancer were screened by bioinformatics methods to explore their expression level,pathogenesis,immune infiltration,mutation and prognosis,and to further explore the potential traditional Chinese medicine for targeted treatment of liver cancer.The differentially expressed genes (DEGs) in normal and hepatoma tissues were analyzed by data set GSE19665;Go and KEGG analysis were performed on DEGs to construct the interaction network of DEGs protein and screen the key genes of liver cancer;Mutation,immune infiltration,expression and prognosis of key genes were analyzed;Excavate potential traditional Chinese medicine and natural active ingredients for the treatment of liver cancer.159 significant DEGs were screened,which were mainly involved in immune and inflammatory responses and involved in p53,mTOR and other signal pathways;Ten key genes were screened out.The expression of four genes such as CDC20 in HCC was significantly increased,and the overall survival time of patients in the high expression group was significantly reduced;The overall survival and disease-free survival of patients with key gene mutations were significantly reduced;The expression of key genes was closely related to the infiltration of immune cells;36 kinds of traditional Chinese medicine and 105 kinds of active ingredients were screened by the key gene target.In this study,the key pathogenic genes of liver cancer were identified,and their abnormal expression was closely related to the poor prognosis and immune cell infiltration of liver cancer.The potential traditional Chinese medicine and its active ingredients for the treatment of liver cancer were excavated.The research results can provide a scientific basis for the diagnosis,treatment and prognosis of liver cancer.

Key words: liver cancer, core gene, bioinformatics, clinical prognosis, immune cell infiltration, traditional Chinese medicine

中图分类号:  R285