转化生长因子β1诊断肝癌和肝癌监测转移的临床价值

目的观察肝癌发生过程中TGFβ1及基因动态表达的临床价值。方法以2-乙酰氨基芴（2-FFA）喂饲雄性SD鼠诱发肝细胞癌变，以病理学方法、巢式RT-PCR、免疫组织化学法和ELISA，观察肝细胞形态学、TGFβ1 mRNA、TGFβ1胞内定位、肝组织及外周血TGFβ1的动态变化与临床价值。结果SD鼠在喂饲2-FAA后，肝细胞出现颗粒样变性、不典型增生到肝癌形成。肝和血TGFβ1：正常组分别为（1．97±0．28）ng／mg和（5．98±1．76）ng／ml，变性组分别为（2．56±0、31）ng／mg和（9、41±0．37）ng／ml，癌前组分别为（3．88±0．11）ng／mg和（12．89±0、69）ng／ml，癌变组分别为（6、74±1．41）ng／mg和（16．74±2．19）ng／ml。癌变组明显高于对照组、肝细胞变性组和癌前病变组。癌变过程中TGFβ1阳性表达呈胞内分布，肝和外周血中TGFβ1呈显著正相关。肝癌患者血浆TGFβ1诊断肝癌的阳性率为89、5％，在血AFP〈400μg／L肝癌患者中，TGFβ1阳性率为93．3％，与AFP联合检查诊断肝癌阳性率达94．7％。肝癌组织TGFβ1 mRNA呈强阳性表达，伴有肝外转移患者外周血TGFβ1 mRNA检出率为100．0％。结论TGFβ1参与肝细胞癌变过程，TGFβ1及TGFβ1 mRNA过表达有助于肝癌早期诊断及预后判断。

An evaluation of transforming growth factor-beta 1 in diagnosing hepatocellular carcinoma and metastasis

OBJECTIVE: To investigate the dynamic expressions of TGF-beta 1 and TGF-beta 1 mRNA at different stages of hepatocellular carcinoma (HCC) development and their use in clinical diagnosis. METHODS: Hepatoma models were developed with 2-FAA using male Sprague-Dawley (SD) rats. Morphological changes of the rat liver histological preparations (H and E stained) were studied. The fragment of TGF-beta 1 gene obtained was amplified by nested RT-PCR. Dynamic change of TGF-beta 1 level was quantitatively analyzed by ELISA. The distribution of TGF-beta 1 in the cells and its gene expression were detected in human HCC tissues. RESULTS: The progressive increases of hepatic TGF-beta 1 and TGF-beta 1 mRNA were observed in rat hepatocytes which progressed from granular degeneration, atypical hyperplasia and finally to HCC development induced by 2-FAA. The expression levels in HCC tissues were significantly higher than those in the normal and degenerative ones. TGF-beta 1 was shown in rat hepatocytes by immunohistochemistry. Plasma TGF-beta 1 was detected in 89.5% of all the patients with HCC, but it was detected in 93.3% of them who had an AFP less than 400 microg/L. TGF-beta 1 mRNA showed a stronger expression in HCC tissues. TGF-beta 1 mRNA was found in peripheral blood mononuclear cells from all HCC patients with extrahepatic metastasis. CONCLUSION: TGF-beta 1 may participate in hepatocyte canceration. The overexpression of TGF-beta 1 and TGF-beta 1 mRNA could be useful markers for early diagnosis and predicting prognosis of HCC.