Shengbing Zang, Feng Liu Jing, Bin Wang, Lingyun Gao, Aimin Huang
Department of Pathology and Institute of Oncology, Fujian Medical University, Fuzhou, Fujian, China.
Anat Rec (Hoboken). 2009 Aug;292(8):1128-34. doi: 10.1002/ar.20950.
KiSS-1 has been identified as a putative metastasis-suppressor gene in human melanomas and breast cancer cell lines. Although loss of KiSS-1 expression has been associated with progression and poor prognosis of various cancers, the exact role of KiSS-1 expression in HCC is not well-defined. Our study investigated KiSS-1 expression levels in HCC and its role in invasion and metastasis of human HCC. The expression levels of KiSS-1 and MMP-9 protein were determined by tissue microarray (TMA) serial sections, immunohistochemistry and semi-quantitative image analysis. All clinical and histological data obtained were subjected to statistical analysis. The expression of KiSS-1 protein in HCC and intrahepatic metastasis lesions was significantly lower (P < 0.01) when compared with non-tumor liver tissue and normal liver tissue. Multivariate analysis revealed a significant inverse correlation between KiSS-1 expression and o1 TNM stage, (F = 7.113, P < 0.01) and o2 intrahepatic metastasis (t = 2.898, P < 0.01). Loss of KiSS-1 in intrahepatic metastasis versus primary carcinomas was statistically significant (P<0.01). We also found a negative correlation between KiSS-1 and MMP-9 expression in HCC (r = -0.506, P < 0.01). We conclude that loss of KiSS-1 during HCC metastasis, along with a concomitant upregulation of MMP-9 suggests a possible mechanism for cell motility and invasion during HCC metastasis, with KiSS-1 emerging as a possible therapeutic target during HCC metastasis.
KiSS-1已被确定为人类黑色素瘤和乳腺癌细胞系中的一种假定转移抑制基因。尽管KiSS-1表达缺失与多种癌症的进展和不良预后相关，但KiSS-1表达在肝癌中的具体作用尚不明确。我们的研究调查了肝癌中KiSS-1的表达水平及其在人类肝癌侵袭和转移中的作用。通过组织芯片（TMA）连续切片、免疫组织化学和半定量图像分析来测定KiSS-1和MMP-9蛋白的表达水平。对获得的所有临床和组织学数据进行统计分析。与非肿瘤肝组织和正常肝组织相比，肝癌组织及肝内转移灶中KiSS-1蛋白的表达显著降低（P < 0.01）。多因素分析显示，KiSS-1表达与TNM分期（F = 7.113，P < 0.01）及肝内转移（t = 2.898，P < 0.01）呈显著负相关。肝内转移灶与原发癌相比，KiSS-1缺失具有统计学意义（P<0.01）。我们还发现肝癌中KiSS-1与MMP-9表达呈负相关（r = -0.506，P < 0.01）。我们得出结论，肝癌转移过程中KiSS-1缺失，同时伴有MMP-9上调，提示这可能是肝癌转移过程中细胞运动和侵袭的一种机制，KiSS-1可能成为肝癌转移过程中的一个治疗靶点。
