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Oncofetal antigen glypican-3 as a promising early diagnostic marker for hepatocellular carcinoma |
Min Yao, Deng-Fu Yao, Yin-Zhu Bian, Chong-Guo Zhang, Li-Wei Qiu, Wei Wu, Wen-Li Sai, Jun-Ling Yang and Hai-Jian Zhang |
Nantong, China
Author Affiliations: Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, China (Yao M, Yao DF, Qiu LW, Wu W, Sai WL, Yang JL and Zhang HJ); Department of Oncology, Yancheng First People s Hospital, Yancheng 224001, China (Bian YZ); Department of Oncology, Second Affiliated Hospital, Nanjing Medical University, Nanjing 210011, China (Zhang CG)
Corresponding Author: Deng-Fu Yao, MD, PhD, Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, China (Tel: 86-513-85052297; Fax: 86-513-85052254; Email: yaodf@ahnmc.com) |
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Abstract BACKGROUND: Hepatocellular carcinoma (HCC) is characterized by a multi-cause, multi-stage and multi-focus process of tumor progression. Its prognosis is poor and early diagnosis is of utmost importance. This study was undertaken to investigate the dynamic expression of oncofetal antigen glypican-3 (GPC-3) and GPC-3 mRNA in hepatocarcinogenesis and to explore their early diagnostic value for HCC.
METHODS: A hepatoma model was induced in male Sprague-Dawley rats with 0.05% 2-fluorenylacetamide and confirmed by hematoxylin and eosin staining and gamma-glutamyltransferase (GGT) expression. Total RNA was purified and transcribed into cDNA by reverse transcription. Fragments of the GPC-3 gene were amplified by nested RT-PCR, and confirmed by sequencing. GPC-3 was analyzed by immunohistochemistry, Western blotting or ELISA.
RESULTS: Positive GPC-3 expression showed as brown granule-like staining localized in the cytoplasm. Histological examination of hepatocytes revealed three morphological stages of granule-like degeneration, atypical hyperplasia (precancerous), and cancer formation, with a progressive increase of liver total RNA and GGT expression. The incidence of liver GPC-3 mRNA and GPC-3, and serum GPC-3 was 100%, 100% and 77.8% in the HCC group, 100%, 100%, and 66.7% in the precancerous group, 83.3%, 83.3%, and 38.9% in the degeneration group, and no expression in the liver or blood of the control group, respectively. There was a positive correlation between liver GPC-3 mRNA and total RNA level (r=0.475, P<0.05) or liver GPC-3 (r=1.0, P<0.001) or serum GPC-3 (r= 0.994, P<0.001).
CONCLUSION: Abnormal oncofetal antigen GPC-3 and GPC-3 mRNA expression in hepatocarcinogenesis may be promising molecular markers for early diagnosis of HCC.
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