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

Abstract

The prognostic assessment of patients with hepatocellular carcinoma (HCC) after resection is an important clinical issue. The present study investigated those genes associated with high serum alpha-fetoprotein (AFP), and their clinical significance, including prognosis and recurrence after hepatectomy. Based on gene expression analysis of 110 training HCC cases, 20 genes whose mRNA expression levels were significantly upregulated and 50 genes that were downregulated correlated with high serum AFP-associated HCC patients. Gene expression profiles of Villin1 (Vil1) were obtained in high serum AFP-associated HCC tumor tissues. In the present analysis, only VIL1 was significantly correlated with the recurrence of HCC. The results were validated independently using Taqman gene expression assays and immunostaining analysis. Results showed that the upregulation of VIL1 mRNA was also correlated with high serum PIVKAII, vascular invasion (P < 0.05), poor differentiation, an advanced cancer stage (P < 0.01) and recurrence-free survival (P = 0.017). The upregulation of VIL1 mRNA 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 AFP levels (overall survival, HR 1.675, P = 0.002; FRS, HR 1.359, P = 0.039) and Vil1 protein expression (overall survival, HR 0.253, P = 0.009; FRS, HR 0.401, P = 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 AFP-associated HCC and a predictive candidate for the postoperative recurrence and poorer prognosis of HCC. (Cancer Sci 2012; 103: 1493-1501 H epatocellular carcinoma (HCC) is the sixth most common cancer in the world, and the 5-year survival rate of individuals with HCC is lower than 10%.(1,2) The prognosis of HCC patients remains dismal, and novel diagnostic modalities as well as improvements in therapeutic strategies currently in use are crucial to improve the clinical outcome for HCC patients. Surgical resection is not the only curative treatment for HCC. Liver transplant is another option for selected patients; however, the rapid recurrence of these tumors is observed frequently, even after apparently curative resections. (3,4) In ten years, various molecules have been proposed as predictive markers for the recurrence of HCC, but none have proved useful clinically, because different patterns of recurrence have not been considered. (5,6) In Tanaka et al.,we report that aberrant Aurora B expression in primary HCC might be a predictive factor of HCC recurrence exceeding the Milan criteria after a curative hepatectomy.The risk factors of recurrence after a curative resection for macroscopic vascular invasion negative hepatocellular carcinoma are closely related to serum alpha-fetoprotein (AFP) levels, multiple tumor formation and non-anatomic hepatic resection. Network expression analysis revealed that dist...

A quantitative proteomics study on olfactomedin 4 in the development of gastric cancer

“…VIL1 was useful for distinguishing normally differentiated epithelial cells from the simple epithelia lining the gastrointestinal tract (41). Upregulation of VIL1 was observed in HCC tissues (42). VIL1 may be a biomarker of metastatic adenocarcinomas.…”

Dysregulated H3K27 Acetylation Is Implicated in Fatty Liver Hemorrhagic Syndrome in Chickens

“…Among these DEGs, 151 were upregulated and 292 were downregulated in FLHS chickens compared to healthy hens. The top 10 upregulated and downregulated genes are indicated in Figure 2B , including OVCH2 ( Wang and Ma, 2019 ), ANKRD22 ( Yin et al, 2017 ), ENSGALG00000005043 ( Moreira et al, 2018 ), SLC6A9 ( Alfadhel et al, 2016 ), NMRAL1 ( Garciandia and Suarez, 2013 ), RASGRP3 ( Oh-hora et al, 2003 ), SLC38A1 ( Kondoh et al, 2007 ), ANGPTL4 ( La Paglia et al, 2017 ; Singh et al, 2018 ), AOC1 ( Iffiu-Soltesz et al, 2010 ), PDE4D ( Yun et al, 2016 ), ADAMTS17 ( Mead and Apte, 2018 ), VIL1 ( Xieraili et al, 2012 ; Roy et al, 2018 ), FAH ( Grompe, 2017 ), and SPON2 ( Zhang Y. L. et al, 2018 ), which have been reported as involved in the regulation of inflammatory processes and lipid metabolism ( Table 2 ).…”

Changes in glucose-6-phosphate dehydrogenase expression results in altered behavior of HBV-associated liver cancer cells

“…Upregulation of villin-1 in high serum ␣-fetoprotein-associated HCC tumor tissues has been correlated with high serum PIVKAII, poor differentiation, vascular invasion, an advanced stage of cancer, and the absence of recurrence. Patients with early HCC recurrence displayed upregulated villin-1 more frequently than patients with late recurrence (49). Considering the known functions of villin-1, it likely takes part in the development of HCC and could be as a marker of postoperative recurrence and poor prognosis of HCC.…”