Villin 1 is a predictive factor for the recurrence of high serum alpha‐fetoprotein‐associated hepatocellular carcinoma after hepatectomy

<jats:p>The prognostic assessment of patients with hepatocellular carcinoma (<jats:styled-content style="fixed-case">HCC</jats:styled-content>) after resection is an important clinical issue. The present study investigated those genes associated with high serum alpha‐fetoprotein (<jats:styled-content style="fixed-case">AFP</jats:styled-content>), and their clinical significance, including prognosis and recurrence after hepatectomy. Based on gene expression analysis of 110 training HCC cases, 20 genes whose <jats:styled-content style="fixed-case">mRNA</jats:styled-content> expression levels were significantly upregulated and 50 genes that were downregulated correlated with high serum <jats:styled-content style="fixed-case">AFP</jats:styled-content>‐associated <jats:styled-content style="fixed-case">HCC</jats:styled-content> patients. Gene expression profiles of Villin1 (Vil1) were obtained in high serum <jats:styled-content style="fixed-case">AFP</jats:styled-content>‐associated <jats:styled-content style="fixed-case">HCC</jats:styled-content> tumor tissues. In the present analysis, only <jats:styled-content style="fixed-case">VIL</jats:styled-content>1 was significantly correlated with the recurrence of <jats:styled-content style="fixed-case">HCC</jats:styled-content>. The results were validated independently using Taqman gene expression assays and immunostaining analysis. Results showed that the upregulation of <jats:styled-content style="fixed-case">VIL</jats:styled-content>1 <jats:styled-content style="fixed-case">mRNA</jats:styled-content> was also correlated with high serum <jats:styled-content style="fixed-case">PIVKAII,</jats:styled-content> vascular invasion (<jats:italic>P</jats:italic> < 0.05), poor differentiation, an advanced cancer stage (<jats:italic>P</jats:italic> < 0.01) and recurrence‐free survival (<jats:italic>P</jats:italic> = 0.017). The upregulation of <jats:styled-content style="fixed-case">VIL</jats:styled-content>1 <jats:styled-content style="fixed-case">mRNA</jats:styled-content> was observed more frequently in the early recurrence patients as compared to the late recurrence patients. Cox regression univariate and multivariate analyses indicated that high serum <jats:styled-content style="fixed-case">AFP</jats:styled-content> levels (overall survival, <jats:styled-content style="fixed-case">HR</jats:styled-content> 1.675, <jats:italic><jats:styled-content style="fixed-case">P</jats:styled-content></jats:italic> = 0.002; <jats:styled-content style="fixed-case">FRS, HR</jats:styled-content> 1.359, <jats:italic><jats:styled-content style="fixed-case">P</jats:styled-content></jats:italic> = 0.039) and Vil1 protein expression (overall survival, <jats:styled-content style="fixed-case">HR</jats:styled-content> 0.253, <jats:italic><jats:styled-content style="fixed-case">P</jats:styled-content></jats:italic> = 0.009; <jats:styled-content style="fixed-case">FRS</jats:styled-content>,<jats:styled-content style="fixed-case"> HR</jats:styled-content> 0.401, <jats:italic><jats:styled-content style="fixed-case">P</jats:styled-content></jats:italic> = 0.041) were independent, unfavorable prognostic factors for overall and recurrence‐free survival of patients. We demonstrated that the VIL1 gene is a potential candidate molecular marker for high serum <jats:styled-content style="fixed-case">AFP</jats:styled-content>‐associated <jats:styled-content style="fixed-case">HCC</jats:styled-content> and a predictive candidate for the postoperative recurrence and poorer prognosis of HCC. (<jats:italic>Cancer Sci</jats:italic>, doi: <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" xlink:href="10.1111/j.1349-7006.2012.02315.x">10.1111/j.1349‐7006.2012.02315.x</jats:ext-link>, 2012)</jats:p>