Role of expression of focal adhesion kinase in progression of hepatocellular carcinoma
Role of expression of focal adhesion kinase in progression of hepatocellular carcinoma
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DOI：
10.1158/1078-0432.ccr-1046-03
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发表时间：
2004-04-15
影响因子：
11.5
通讯作者：
Maehara, Y
中科院分区：
文献类型：
--
作者：
Itoh, S;Maeda, T;Maehara, Y
目的：虽然肝细胞癌（HCC）是人类肝脏最常见的癌症，但调控HCC发生和进展的机制仍不清楚。本研究的目的是调查是否粘着斑激酶（FAK）参与人类hcz.Experimental设计的进展：FAK蛋白质印迹分析进行了三个肝癌细胞系。我们回顾了64例未经术前治疗的原发性肝癌患者。对石蜡包埋组织进行FAK免疫组化分析。FAK表达在几个临床样品中通过Western印迹分析证实。我们研究了FAK表达与临床结果之间的相关性。结果：所有肝癌细胞系均检测到FAK蛋白。正常肝和慢性肝炎伴或不伴肝硬化的肝细胞FAK表达免疫组化染色阴性。64例中18例（28.1%）胞浆FAK阳性表达，其阳性表达与性别（P < 0.05）、血清白蛋白水平（P <0.05）、门静脉侵犯（P < 0.01）有关。FAK阳性表达与生存率显著相关（P < 0.05）。在多因素分析中，FAK过表达是决定患者预后的独立因素。结论：FAK在HCC中促进肿瘤进展，尤其是血管浸润方面起重要作用。FAK可能在HCC的进展中发挥重要作用，并将成为HCC治疗的新靶点以及预后标志物。
Purpose: Although hepatocellular carcinoma (HCC) is the most common cancer of the human liver, the mechanisms that regulate HCC development and progression remain unclear. The aim of this study was to investigate whether focal adhesion kinase (FAK) is involved in the progression of human HCC.Experimental Design: Western blot analysis for FAK was performed on three HCC cell lines. We reviewed 64 consecutive patients who had undergone initial liver resection for HCC without preoperative treatment. Immunohistochemistry analysis for FAK was performed on paraffin-embedded tissues. FAK expression was confirmed by Western blot analysis in several clinical samples. We investigated the correlation between FAK expression and clinical outcome. Results: FAK proteins were detected in all HCC cell lines. Hepatocytes in the normal liver and chronic hepatitis with or without cirrhosis were negative for immunohistochemical staining for FAK expression. Cytoplasmic FAK expression was observed in 18 of 64 patients (28.1%), and this positive staining was correlated with gender (P < 0.05), a lower level of serum albumin (P < 0.05), and portal venous invasion (P < 0.01). Positive staining for FAK was associated with significantly poorer survival (P < 0.05). In multivariate analysis, FAK overexpression was an independent factor in determining the prognosis of patients.Conclusions: These data suggest that FAK plays an important role in promoting tumor progression, especially vascular invasion, in HCC. FAK could play an important role in HCC progression and would be a novel target for HCC therapeutics as well as a prognostic marker.