Abstract
BackgroundLiver cancr is a heterogeneous disease in terms of etiology, biologic and clinical behavior. Very little is known about how many genes concur at the molecular level of tumor development, progression and aggressiveness. To explore the key genes involved in the development of liver cancer, we established a rat model induced by diethylnitrosamine to investigate the gene expression profiles of liver tissues during the transition to cirrhosis and carcinoma.MethodsA rat model of liver cancer induced by diethylnitrosamine was established. The cirrhotic tissue, the dysplasia nodules, the early cancerous nodules and the cancerous nodules from the rats with lung metastasis were chosen to compare with liver tissue of normal rats to investigate the differential expression genes between them. Affymetrix GeneChip Rat 230 2.0 arrays were used throughout. The real-time quantity PCR was used to verify the expression of some differential expression genes in tissues.ResultsThe pathological changes that occurred in the livers of diethylnitrosamine-treated rats included non-specific injury, fibrosis and cirrhosis, dysplastic nodules, early cancerous nodules and metastasis. There are 349 upregulated and 345 downregulated genes sharing among the above chosen tissues when compared with liver tissue of normal rats. The deregulated genes play various roles in diverse processes such as metabolism, transport, cell proliferation, apoptosis, cell adhesion, angiogenesis and so on. Among which, 41 upregulated and 27 downregulated genes are associated with inflammatory response, immune response and oxidative stress. Twenty-four genes associated with glutathione metabolism majorly participating oxidative stress were deregulated in the development of liver cancer. There were 19 members belong to CYP450 family downregulated, except CYP2C40 upregulated.ConclusionIn this study, we provide the global gene expression profiles during the development and progression of liver cancer in rats. The data obtained from the gene expression profiles will allow us to acquire insights into the molecular mechanisms of hepatocarcinogenesis and identify specific genes (or gene products) that can be used for early molecular diagnosis, risk analysis, prognosis prediction, and development of new therapies.
Highlights
Liver cancr is a heterogeneous disease in terms of etiology, biologic and clinical behavior
In this study, we provide the global gene expression profiles during the development and progression of liver cancer in rats
The data obtained from the gene expression profiles will allow us to acquire insights into the molecular mechanisms of hepatocarcinogenesis and identify specific genes that can be used for early molecular diagnosis, risk analysis, prognosis prediction, and development of new therapies
Summary
Liver cancr is a heterogeneous disease in terms of etiology, biologic and clinical behavior. To explore the key genes involved in the development of liver cancer, we established a rat model induced by diethylnitrosamine to investigate the gene expression profiles of liver tissues during the transition to cirrhosis and carcinoma. HCC is a heterogeneous disease in terms of etiology, biologic and clinical behavior. Hepatocarcinogenesis is a long-term, multistep process associated with changes in gene expression profiles. In the last several years, there have been important gains in our understanding of the pathogenesis of HCC and our appreciation of the critical oncogenic and tumor suppressor pathways involved in hepatocarcinogenesis [1,2,3,4,5]. Molecular profiling has been successfully used to identify candidate genes for HCC in human and animal model systems[3]. Animal models of carcinogenesis have permitted the examination of the stages of neoplastic development in considerable detail
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