机构地区:[1]福建医科大学基础医学院病理学系 福建医科大学肿瘤研究室,福州350004 [2]福建医科大学附属第一医院肝脏外科
出 处:《中华肝胆外科杂志》2011年第3期223-227,共5页Chinese Journal of Hepatobiliary Surgery
基 金:基金项目:教育部科学技术研究重点项目(205077);福建省教育厅科技项目(JA04193,JS06011)
摘 要:目的检测肿瘤转移抑制基因KiSS-1及其配体KiSS-1R和基质金属蛋白酶-9(MMP-9)在肝细胞癌(HCC)中的表达,探讨KISS-1表达与肝细胞癌侵袭转移的关系及其机制。方法利用逆转录聚合酶链反应(RT—PCR)技术,检测HCC、癌旁肝组织及远癌肝组织中KISS-1、KiSS-1RmRNA的表达情况;应用HCC组织芯片,结合免疫组化及彩色图像分析技术检测了KiSS-1、MMP-9蛋白在HCC芯片中各组织的相对表达量。结果KiSS-1mRNA在HCC中表达明显低于癌旁、远癌肝组织(P〈0.01)。在转移组和临床Ⅲ期HCC中,KiSS-1蛋白的表达明显低于无转移及临床分期I和Ⅱ期HCC(P〈0.01);KiSS-1在肝内转移灶中的表达量显著低于原发灶(P〈0.01)。在转移组的HCC中,MMP-9表达量显著高于无转移的HCC(P〈0.01)。在HCC组织中,KiSS-1和MMP-9的表达呈负相关性(r=-0.340,P〈0.01)。结论KiSS I和MMP-9的表达失衡与HCC侵袭转移有关,KiSS-1的缺失表达可作为预测HCC转移潜能的有价值的参考指标。Objective To detect the expression of KISS-1 , KiSS-1R and MMP-9 in hepatocellular carcinoma (HCC). To study the correlation of KISS-1 , KiSS-1R and MMP-9 expression with invasion and metastasis of HCC, and to explore the underlying mechanisms. Methods The expression of KISS-1 , KiSS-IR mRNA in 33 HCC samples, 26 non-neoplastic adjacent liver tissue samples and 13 non-neoplastic distant liver tissue samples were detected by RT-PCR. Tissue chips were constructed by modified manual tools, which contained HCC, non-neoplastic adjacent liver tissues, non-neoplastic distant liver tissues, normal liver tissues and intrahepatic metastasis lesions. The expression of KISS-1 and MMP-9 protein was determined by tissue chips, immunohistochemistry and semi-quantitative image analysis in 150 HCC, 137 non-neoplastic adjacent liver tissue, 98 non-neoplastic distant liver tissues, 16 normal liver tissues and 37 intrahepatic metastasis lesion samples. Results The results of RT-PCR showed that compared with the non-neoplastic adjacent liver tissues and the non-neoplastic distant liver tissues, the expression of KISS-1 mRNA in HCC was significantly lower (P〈0.01). The expression of KiSS-1R mRNA did not changed in HCC and non-neoplastic liver tissues (P〉0.05). The expression of KISS-1 protein was lower in HCC with metastasis and in clinical stage III than that in those with non-metastasis, and in clinical stages I and II. It was also higher in the primary than in the metastasis lesions (P〈0.01, respectively). The expression of MMP-9 was higher in tumors having peplos invasion and metastasis than in those with negative peplos invasion and non-metastasis. It was lower in the primary than the metastasis lesions (P〈0. 01, respectively). Negative correlation between KISS-1 and MMP-9 expression was found in HCC(r=- 0. 340, P〈0.01). Conclusions The imbalance between KISS-1 and MMP-9 expression might play an important role in enhancing the invasive and metastatic capacity of HCC. Loss of KISS-1 expression mig
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