Snail accelerates cancer invasion by upregulating MMP expression and is associated with poor prognosis of hepatocellular carcinoma

Abstract

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 ¼ 0.047). In the ordinary HCC tissues, Snail expression was significantly correlated with portal vein invasion (P ¼ 0.035) and intrahepatic metastasis (P ¼ 0.050); it also showed a significant correlation with MT1-MMP expression (r ¼ 0.572, Po0.001). In recurrence-free survival, the group with high Snail expression showed significantly poorer prognosis (P ¼ 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. British Journal of Cancer (2005) Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies in the world and a frequent cause of cancer fatalities in Japan. Improvements in early diagnosis, surgical techniques, and perioperative management have contributed to decreases in mortality and morbidity among patients with HCC (Okuda et al, 1985;Fran et al, 1999). However, the long-term prognosis of patients with HCC after hepatectomy has been still poor because of a high incidence of recurrence after initial treatment (Fong et al, 1999;Poon et al, 2000b). Several centres have reported a cumulative 5-year recurrence rate ranging from 75 to 100% (Chen et al, 1994;Fong et al, 1999;Poon et al, 2000b). Pathological and genetic analyses have indicated two features in HCC recurrence: multicentric occurrence of new tumours (MO) and intrahepatic metastasis of the original tumour (im) (Tsuda et al, 1992;Matsumoto et al, 2001). It has been reported that MO is significantly influenced by the underlying liver status, such as the presence of active hepatitis (Belghiti et al, 1991;Ko et al, 1996). On the other hand, im is thought to be more closely associated with tumour factors, especially portal vein invasion (vp) (Vauthey et al, 1995;Shimada et al, 1999). Several published studies have demonstrated that vp plays an important role in the im process and influences the survival rate of patients with HCC (Fuster et al, 1996;Mitsunobu et al, 1996; The Liver Cancer Study Group of Japan, 1994). Therefore, it is important to elucidate the molecular mechanisms of vp and im; the subsequent establishment of markers for predicting vp and im may contribute to improvement in the prognosis of patients with HCC.Recently, the z...

Collagen type I-induced Smad-interacting protein 1 expression downregulates E-cadherin in pancreatic cancer

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Snail Family Transcription Factors Are Implicated in Thyroid Carcinogenesis

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Transforming Growth Factor-β1-Mediated Slug and Snail Transcription Factor Up-Regulation Reduces the Density of Langerhans Cells in Epithelial Metaplasia by Affecting E-Cadherin Expression

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