Journal
HEPATOLOGY
Volume 70, Issue 1, Pages 184-197Publisher
WILEY
DOI: 10.1002/hep.30581
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Categories
Funding
- Ministry of Science and Technology [MOST 103-2314-B-002-163, MOST 104-2314-B-002-069, MOST 105-2314-B-002-115-MY2, MOST 106-2314-B-002-096-MY3, MOST 107-3017-F-002-002]
- Ministry of Health and Welfare, Executive Yuan
- National Taiwan University, National Taiwan University Hospital [NTUH107-S3773]
- Liver Disease Prevention and Treatment Research Foundation, Taiwan
- Center of Precision Medicine from the Featured Areas Research Center Program within the Higher Education Sprout Project by the Ministry of Education (MOE) in Taiwan [NTU-107L9014-1]
- Ministry of Education (MOE) in Taiwan [NTU-107L9014-1]
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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.
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