Snail accelerates cancer invasion by upregulating MMP expression and is associated with poor prognosis of hepatocellular carcinoma.
We have previously demonstrated in an in vitro study that Snail increased the invasion activity of hepatoma cells by upregulating matrix metalloproteinase (MMP) gene expression. In the present study, we examined whether Snail gene expression correlates with cancer invasion and prognosis of patients with hepatocellular carcinoma (HCC). Quantitative reverse transcription-polymerase chain reaction (RT-PCR) was performed to evaluate Snail, E-cadherin, and MMP mRNA expressions in eight nodule-in-nodule tumours and 47 ordinary HCC tissues. In the nodule-in-nodule tumours, Snail expression significantly increased with tumour dedifferentiation (P=0.047). In the ordinary HCC tissues, Snail expression was significantly correlated with portal vein invasion (P=0.035) and intrahepatic metastasis (P=0.050); it also showed a significant correlation with MT1-MMP expression (r=0.572, P<0.001). In recurrence-free survival, the group with high Snail expression showed significantly poorer prognosis (P=0.035). Moreover, high Snail expression was an independent risk factor for early recurrence after curative resection. During the progression of HCC, Snail expression may be induced and accelerate invasion activity by upregulating MMP expression, resulting in portal invasion, intrahepatic metastasis, and poor prognosis.
Miyoshi
A
A
Department of Surgery, Saga University Faculty of Medicine, 5-1-1 Nabeshima, Saga 849-8501, Japan.
Kitajima
Y
Y
Kido
S
S
Shimonishi
T
T
Matsuyama
S
S
Kitahara
K
K
Miyazaki
K
K
D000368:Aged; D000369:Aged, 80 and over; D015820:Cadherins / Q000096:biosynthesis; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008297:Male; D020782:Matrix Metalloproteinases / Q000096:biosynthesis*; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology*; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000096:biosynthesis*; D015854:Up-Regulation
D015820:Cadherins; D004268:DNA-Binding Proteins; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D020782:Matrix Metalloproteinases