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| Clinical impact of plasma TGF-β1 and circulating TGF-β1 mRNA in diagnosis of hepatocellular carcinoma |
| Zhi-Zhen Dong, Deng-Fu Yao, Min Yao, Li-Wei Qiu, Lei Zong, Wei Wu, Xin-Hua Wu, Deng-Bing Yao and Xian-Yong Meng |
Nantong, China
Author Affiliations: Department of Diagnostics (Dong ZZ), Research Center of Clinical Molecular Biology (Yao DF, Qiu LW, Zong L, Wu W and Wu XH), Department of Laboratory Science (Yao M), and Department of Gastroenterology (Meng XY), Affiliated Hospital; and Institute of Neurosciences (Yao DB), Nantong University, Nantong 226001, China
Corresponding Author: Deng-Fu Yao, MD, PhD, Research Center of Clinical Molecular Biology, Affiliated Hospital, Nantong University, Nantong 226001, China (Tel: 86-513-85052413; Fax: 86-513-85052523; Email: yaodf@ahnmc.com) |
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Abstract BACKGROUND: Transforming growth factor-β (TGF-β) plays an important role in the regulation of cell growth and differentiation, angiogenesis, extracellular matrix formation, immunosuppression and cancer development. In this study, we investigated the levels of TGF-β1 and TGF-β1 mRNA expression, their relationship with HBV replication, and their diagnostic value for hepatocellular carcinoma (HCC).
METHODS: Total RNAs were extracted from HCC samples and matched non-tumor tissues, and from peripheral blood mononuclear cells in HCC patients. TGF-β1 mRNA was amplified by RT-PCR and confirmed by DNA sequencing. The distribution of TGF-β1 expression was assessed by immunohistochemistry. The clinical characteristics were analyzed between TGF-β1 and HBV replication. The diagnostic value of circulating TGF-β1 and TGF-β1 mRNA levels were investigated in HCC patients.
RESULTS: The incidence of hepatic TGF-β1 expression was 83.3% in HCC samples, 43.3% in the surrounding tissues, 94.7% in the HBV DNA-positive group, and 63.6% in the HBV DNA-negative group. Liver TGF-β1 expression was associated with the degree of HCC differentiation and the status of HBV replication, but not with the size or number of tumors. Circulating TGF-β1 level and incidence of TGF-β1 mRNA were significantly higher in the HCC group than in any group of patients with benign liver disease, with a higher sensitivity of 89.5% and a specificity of 94.0% for HCC diagnosis when circulating TGF-β1 levels were >1.2 µg/L. No significant correlation was found between TGF-β1 expression and AFP level or tumor size. Combining TGF-β1 level and serum AFP raised the detection rate to 97.4%.
CONCLUSIONS: Abnormal expression of hepatic TGF-β1 is associated with the degree of HCC differentiation and HBV replication. Both circulating TGF-β1 and TGF-β1 mRNA can be used as sensitive biomarkers for the diagnosis and prognosis of HBV-induced HCC.
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2008, Vol. 7 
