KiSS-1、KiSS-1R及MMP-9表达与肝细胞癌侵袭转移的关系及意义

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-1R mRNA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-1 mRNA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-1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.

Abstract：

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-1R 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 might predict an aggressive clinical behavior and was associated with metastatic potential in HCC.

Correlation of KiSS-1, KiSS-1R and MMP-9 expression to invasion and metastasis of hepatocellular carcinoma and its significance

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-1R 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 might predict an aggressive clinical behavior and was associated with metastatic potential in HCC.