Expression of KiSS-1 gene and its role in invasion and metastasis of human hepatocellular carcinoma.
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.
Shengbing
Zang
Z
Department of Pathology and Institute of Oncology, Fujian Medical University, Fuzhou, Fujian, China.
Feng
Liu Jing
LJ
Bin
Wang
W
Lingyun
Gao
G
Aimin
Huang
H
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000502:physiology*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000556:secondary; D018450:Disease Progression; D015536:Down-Regulation; D005260:Female; D015870:Gene Expression; D006801:Humans; D059648:Kisspeptins; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011379:Prognosis; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000502:physiology*
D014408:Biomarkers, Tumor; C106628:KISS1 protein, human; D059648:Kisspeptins; D025521:Tumor Suppressor Proteins; D020780:Matrix Metalloproteinase 9