慢性肝病和肝细胞癌中的转化生长因子-α与表皮生长因子受体

Transforming growth factor-alpha and epidermal growth factor receptor in chronic liver disease and hepatocellular carcinoma.

作者信息

Harada K, Shiota G, Kawasaki H

机构信息

Second Department of Internal Medicine, Tottori University School of Medicine, Yonago, Japan.

出版信息

Liver. 1999 Aug;19(4):318-25. doi: 10.1111/j.1478-3231.1999.tb00056.x.

DOI:10.1111/j.1478-3231.1999.tb00056.x

PMID:10459631

Abstract

AIMS/BACKGROUND: Transforming growth factor-alpha (TGF-alpha) is a potent mitogen of normal and neoplastic hepatocytes. In addition, TGF-alpha has been reported to play a pivotal role in hepatocarcinogenesis. To evaluate the significance of TGF-alpha in chronic liver diseases and hepatocellular carcinoma, we examined serum TGF-alpha, and expression of TGF-alpha, epidermal growth factor receptor (EGFR) and proliferating cell nuclear antigen (PCNA) mRNA in liver tissues.

METHODS

Thirty-five patients with chronic hepatitis (CH), 33 with liver cirrhosis (LC), 55 with hepatocellular carcinoma (HCC) and 53 normal controls (C) were enrolled in this study. Serum TGF-alpha levels were measured by an enzyme-linked immunosorbent assay. Expression of TGF-alpha, EGFR, PCNA and beta-actin mRNA in liver tissues were examined by reverse transcription polymerase chain reaction.

RESULTS

Serum TGF-alpha levels in C, CH, LC and HCC were 5.6+/-2.1, 33.2+/-8.3, 404.0+/-173.0 and 100.3+/-39.2 pg/ml, respectively. Serum TGF-alpha level in LC was higher than in other diseases (p<0.01, compared to CH, HCC and C, respectively). Serum TGF-alpha levels exhibited a significant positive correlation with total bilirubin, ICGR15 and Pugh score (p<0.01, p<0.01 and p<0.05, respectively), and increased in parallel with severity of disease according to Child classification. Although the ratios of TGF-alpha, EGFR and PCNA mRNA to beta-actin mRNA were not significantly different among the diseases, the TGF-alpha/beta-actin ratio correlated with EGFR/beta-actin and PCNA/beta-actin ratios (p<0.001 and p<0.0001, respectively), and EGFR/beta-actin ratio was related to PCNA/beta-actin ratio in all patients, especially with HCC.

CONCLUSION

The results of the present study suggest that serum TGF-alpha levels are closely related to severity of liver dysfunction, and that hepatic expression of TGF-alpha and EGFR correlates with proliferation of normal and neoplastic hepatocytes.

摘要

目的/背景：转化生长因子-α（TGF-α）是正常和肿瘤性肝细胞的一种强效促有丝分裂原。此外，据报道TGF-α在肝癌发生过程中起关键作用。为评估TGF-α在慢性肝病和肝细胞癌中的意义，我们检测了血清TGF-α以及肝组织中TGF-α、表皮生长因子受体（EGFR）和增殖细胞核抗原（PCNA）mRNA的表达。

方法

本研究纳入了35例慢性肝炎（CH）患者、33例肝硬化（LC）患者、55例肝细胞癌（HCC）患者和53例正常对照者（C）。采用酶联免疫吸附测定法检测血清TGF-α水平。通过逆转录聚合酶链反应检测肝组织中TGF-α、EGFR、PCNA和β-肌动蛋白mRNA的表达。

结果

C组、CH组、LC组和HCC组的血清TGF-α水平分别为5.6±2.1、33.2±8.3、404.0±173.0和100.3±39.2 pg/ml。LC组的血清TGF-α水平高于其他疾病组（与CH组、HCC组和C组相比，p<0.01）。血清TGF-α水平与总胆红素、ICGR15和Pugh评分呈显著正相关（分别为p<0.01、p<0.01和p<0.05），并且根据Child分级随疾病严重程度平行升高。尽管不同疾病组中TGF-α、EGFR和PCNA mRNA与β-肌动蛋白mRNA的比值无显著差异，但TGF-α/β-肌动蛋白比值与EGFR/β-肌动蛋白和PCNA/β-肌动蛋白比值相关（分别为p<0.001和p<0.0001），并且在所有患者中，尤其是HCC患者中，EGFR/β-肌动蛋白比值与PCNA/β-肌动蛋白比值相关。