Expression of Metastatic Tumor Antigen 1 Splice Variant Correlates With Early Recurrence and Aggressive Features of Hepatitis B Virus–Associated Hepatocellular Carcinoma
Journal
Hepatology
Journal Volume
70
Journal Issue
1
Pages
184-197
Date Issued
2019
Author(s)
Li Y.-T.
Wu H.-L.
Cheng H.-R.
Wang C.-C.
Abstract
Overexpression of metastatic tumor antigen 1 (MTA1) was correlated with poor prognosis of hepatitis B virus (HBV)-associated hepatocellular carcinoma (HBV-HCC). The aim of this study was to examine the clinical significance of the expression of MTA1 and its exon 4-excluded form (MTA1dE4), the most abundant spliced variant of MTA1, in patients receiving curative resection for HBV-HCC. We collected 102 patients with?HBV-HCC and received curative resection retrospectively and examined the expressions level of total MTA1/MTA1dE4 in their paired nontumor and tumor liver tissues by using RT-qPCR. The association between MTA1/MTA1dE4 expression and various tumor features as well as tumor recurrence was analyzed. During the median follow-up period of 4 years, 25 patients (24.5%) showed early recurrence (within 12 months postresection) and 42 (54.5%) showed late recurrence. In Kaplan-Meier analysis, MTA1dE4 overexpression in tumor, but not MTA1, was associated with early recurrence (P = 0.0365), but not late recurrence. In multivariate analysis, only alpha-fetoprotein (AFP) ?200 ng/mL (P = 0.006) and large tumor size (P = 0.027) were correlated with early recurrence. In the subgroup of patients with AFP <200 ng/mL, high MTA1dE4, but not total MTA1, expression could help predict early recurrence (P = 0.0195). In vitro, wound healing and invasion assays were performed in HCC cells, and MTA1dE4 was found to exhibit a higher ability in promoting migration and invasion of hepatoma cells than full-length MTA1. Conclusion: MTA1dE4 expression is correlated with more aggressive tumor characteristics and might serve as a more sensitive marker for early recurrence of HBV-HCC, especially for low-AFP patients. ? 2019 by the American Association for the Study of Liver Diseases.
Other Subjects
alpha fetoprotein; biological marker; lamivudine; metastatic tumor antigen 1; mta1de4 protein; tumor antigen; unclassified drug; isoprotein; Mta1 protein, human; repressor protein; transactivator protein; tumor marker; adult; antigen expression; Article; cancer prognosis; cell invasion; cell migration; chronic hepatitis B; clinical outcome; controlled study; female; gene overexpression; Hepatitis B virus; histopathology; human; human cell; human tissue; in vitro study; liver cell carcinoma; liver resection; liver tissue; major clinical study; male; middle aged; predictive value; priority journal; protein expression level; quantitative analysis; real time polymerase chain reaction; recurrence risk; retrospective study; risk factor; SK-HEP-1 cell line; tumor number; tumor recurrence; tumor volume; wound healing assay; aged; complication; hepatitis B; liver; liver cell carcinoma; liver tumor; metabolism; pathology; tumor recurrence; virology; Adult; Aged; Biomarkers, Tumor; Carcinoma, Hepatocellular; Female; Hepatitis B; Humans; Liver; Liver Neoplasms; Male; Middle Aged; Neoplasm Recurrence, Local; Protein Isoforms; Repressor Proteins; Retrospective Studies; Trans-Activators
Publisher
John Wiley and Sons Inc.
Type
journal article