Characteristic gene expression profiles in the progression from liver cirrhosis to carcinoma induced by diethylnitrosamine in a rat model.
BACKGROUND
Liver cancer 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.


METHODS
A 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.


RESULTS
The 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.


CONCLUSIONS
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 (or gene products) that can be used for early molecular diagnosis, risk analysis, prognosis prediction, and development of new therapies.
Liu
Yue-Fang
YF
Department of Pathology, Nanjing Medical University, 140 Han Zhong Road, Nanjing 210029, PR China. lyf19054@yahoo.com.cn
Zha
Bin-Shan
BS
Zhang
Hui-Lin
HL
Zhu
Xiao-Jing
XJ
Li
Yu-Hua
YH
Zhu
Jin
J
Guan
Xiao-Hong
XH
Feng
Zhen-Qing
ZQ
Zhang
Jian-Ping
JP
D000477:Alkylating Agents; D000818:Animals; D002273:Carcinogens; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D004052:Diethylnitrosamine; D018450:Disease Progression; D020869:Gene Expression Profiling; D008103:Liver Cirrhosis / Q000235:genetics* / Q000473:pathology; D008113:Liver Neoplasms / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D008297:Male; D023421:Models, Animal; D051381:Rats; D017208:Rats, Wistar
D000477:Alkylating Agents; D002273:Carcinogens; D004052:Diethylnitrosamine