肿瘤转移抑制基因KiSS-1和基质金属蛋白酶-9在肝细胞癌门静脉癌栓中的表达

Expression of Tumor Metastasis-suppressor Gene KiSS-1 and Matrix Metalloproteinase-9 in Portal Vein Tumor Thrombus of Hepatocellular Carcinoma

背景与目的:肿瘤转移抑制基因KiSS-1与恶性肿瘤的转移具有一定关系,但它与肝细胞癌的转移特别是与门静脉癌栓形成的关系罕有报道。本实验探讨KiSS-1基因在门静脉癌栓形成中的作用及机制。方法:应用RT-PCR法和免疫组化方法检测50例肝细胞癌组织及11例门静脉癌栓组织中KiSS-1基因和基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)的表达。结果:门静脉癌栓组、伴癌栓肝细胞癌组、不伴癌栓肝细胞癌组中KiSS-1基因的mRNA阳性率分别为18.2%(2/11)、16.1%(5/31)、63.2%(12/19),蛋白阳性率分别为0%(0/11)、12.9%(4/31)、47.4%(9/19),癌栓组和伴癌栓肝细胞癌组的KiSSmRNA和蛋白阳性率均明显低于不伴癌栓肝细胞癌组(P<0.05),而癌栓组与伴癌栓肝细胞癌组之间的差异无统计学意义(P>0.05)。各组中MMP-9mRNA的阳性率分别为72.7%(8/11)、77.4%(24/31)、31.6%(6/19),MMP-9蛋白的阳性率分别为81.8%(9/11)、83.9%(26/31)、42.1%(8/19),癌栓组与伴癌栓肝细胞癌组的MMP-9mRNA和蛋白阳性率之间差异均无统计学意义(P>0.05),但均明显高于不伴癌栓的肝细胞癌组(P<0.05)。KiSS-1基因与MMP-9的mRNA和蛋白阳性率均呈负相关(r值分别为-0.362、-0.473,P值均<0.05)。结论:KiSS-1基因、MMP-9与门静脉癌栓的形成密切相关,KiSS-1基因可能通过抑制MMP-9表达而抑制门静脉癌栓的形成。

BACKGROUND ＆ OBJECTIVE： Tumor metastasis-suppressor gene KISS-1 is related to the metastasis of malignancies. However, its correlation to the metastasis, especially the formation of portal vein tumor thrombus （PVTT）, of hepatocellular carcinoma （HCC） has seldom been reported. This study was to investigate the function of KISS-1 gene in the formation of PVTT of HCC, and explore the machanism. METHODS： The expression of KISS-1 and matrix metalloproteinase-9 （MMP-9） in 50 specimens of HCC （31 cases with PVTT and 19 cases without PVTT） and 11 specimens of PVTT was detected by reverse transcription-polymerase chain reaction （RT-PCR） and immunohistochemistry （IHC）. RESULTS： The positive rates of KISS-1 mRNA and protein were significantly lower in PVTT group and HCC with PVTT group than in HCC without PVTT group （18.2% and 16.1% vs. 63.2%, 0% and 12.9% vs. 47.4%, P〈0.05）; the positive rates of MMP-9 mRNA and protein were significantly higher in PVTT group and HCC with PVTT group than in HCC without PVTT group （72.7% and 77.4% vs. 31.6%, 81.8% and 83.9% vs. 42.1%, P〈0.05）. There was no significant difference between PVTT group and HCC with PVTT group （P〉0.05）. KISS-1 expression was negatively related to MMP-9 expression （r=-0.362 for mRNA, and r=-0.473 for protein, each P〈0.05）. CONCLUSIONS.. KISS-1 and MMP-9 are closely related to the formation of PVTT. KISS-1 gene might suppress the formation of PVTT by suppressing MMP-9 synthesis.