Transcriptome Analysis Of The Occurrence And Development Of Hepatitis,Fibrosis And Liver Cancer

Background:Liver cancer is a malignant tumor with great harm to human body,difficult to cure and high mortality.Although there are many studies and discoveries on liver related diseases such as hepatocellular carcinoma,which have played a certain role in the treatment and prevention of the disease,there are few molecular related studies on the whole process of liver cancer,that is,from hepatitis to liver fibrosis and finally to liver cancer.Objective and significance:The purpose of this study is to explore the dynamic changes of intracellular transcriptome in the occurrence and development of liver cancer.In this study,we used diethylnitrosamine to induce spontaneous liver cancer in mice,and used the method of population cell transcriptome sequencing of liver samples at various stages in the pathogenesis of hepatocellular carcinoma,so as to explore the dynamic changes of transcriptome of hepatocytes and immune cells in the liver from hepatitis to liver cancer,Reveal the key genes,pathways and microenvironment regulating the occurrence and development of this process,and preliminarily identify the changes of key genes and pathways.To provide scientific data for the treatment of hepatitis,liver fibrosis and liver cancer.Methods:Taking the mouse model of liver cancer induced by diethylnitrosamine as the research object,the transcriptome sequencing of liver samples from healthy,hepatitis,liver fibrosis and hepatocellular carcinoma mice was carried out.The samples of each stage of the disease were screened through pathological detection(diagnostic gold standard).The RNA of liver samples of mice at each disease stage was extracted and the library was constructed.After the quality of the library reached the standard,it was sequenced.After obtaining the corresponding sequencing data,carry out quality control,comparison and differential expression analysis(DEA),GO function enrichment,KEGG analysis,survival analysis and so on.Research contents and results:1)we obtained the transcriptome data of diethylnitrosamine induced hepatitis,liver fibrosis,hepatocellular carcinoma and liver cell population of healthy mice;2)Through the analysis of gene expression differences among liver tissue samples of mouse health,hepatitis,liver fibrosis and liver cancer,the highly expressed genes in various types of samples were obtained.The key genes such as Cthrcl,Sfrp2,Krt20,Slc7a11,Gstal and Stra6 may be related to the occurrence and development of hepatocellular carcinoma;3)Enrichment analysis found differences in pathways and functions among various samples,among which ECM-eceptor interaction extracellular matrix interaction,Cell adhesion molecules(CAMs)and PI3K-Akt signaling pathway were enriched in many comparative combinations in this study.Main conclusion:It is helpful for us to study the transcriptional mechanism of liver cancer induced by nitrosamine in various stages of liver cancer,so as to deepen the study of the transcriptional mechanism of liver cancer cells by sequencing the key genes of liver cancer induced by nitrosamine.The understanding will help us to further explore and find the specific molecular changes and characteristics in the occurrence and development of hepatocellular carcinoma,and promote the clinical prevention and treatment of hepatocellular carcinoma.