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Li, Yung‐Tsung; Wu, Hui‐Lin; Kao, Jia‐Horng; Cheng, Huei‐Ru; Ho, Ming‐Chih; Wang, Chih‐Chiang; Chen, Pei‐Jer; Chen, Ding‐Shinn; Liu, Chun‐Jen

Expression of Metastatic Tumor Antigen 1 Splice Variant Correlates With Early Recurrence and Aggressive Features of Hepatitis B Virus–Associated Hepatocellular Carcinoma

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  • Media type: E-Article
  • Title: Expression of Metastatic Tumor Antigen 1 Splice Variant Correlates With Early Recurrence and Aggressive Features of Hepatitis B Virus–Associated Hepatocellular Carcinoma
  • Contributor: Li, Yung‐Tsung; Wu, Hui‐Lin; Kao, Jia‐Horng; Cheng, Huei‐Ru; Ho, Ming‐Chih; Wang, Chih‐Chiang; Chen, Pei‐Jer; Chen, Ding‐Shinn; Liu, Chun‐Jen
  • imprint: Ovid Technologies (Wolters Kluwer Health), 2019
  • Published in: Hepatology
  • Language: English
  • DOI: 10.1002/hep.30581
  • ISSN: 0270-9139; 1527-3350
  • Keywords: Hepatology
  • Origination:
  • Footnote:
  • Description: <jats:p>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 <jats:italic toggle="yes">MTA1</jats:italic> and its exon 4‐excluded form (<jats:italic toggle="yes">MTA1dE4</jats:italic>), the most abundant spliced variant of <jats:italic toggle="yes">MTA1</jats:italic>, 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 <jats:italic toggle="yes">MTA1</jats:italic>/<jats:italic toggle="yes">MTA1dE4</jats:italic> in their paired nontumor and tumor liver tissues by using RT‐qPCR. The association between <jats:italic toggle="yes">MTA1</jats:italic>/<jats:italic toggle="yes">MTA1dE4</jats:italic> 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, <jats:italic toggle="yes">MTA1dE4</jats:italic> overexpression in tumor, but not <jats:italic toggle="yes">MTA1</jats:italic>, was associated with early recurrence (<jats:italic toggle="yes">P</jats:italic> = 0.0365), but not late recurrence. In multivariate analysis, only alpha‐fetoprotein (AFP) ≥200 ng/mL (<jats:italic toggle="yes">P</jats:italic> = 0.006) and large tumor size (<jats:italic toggle="yes">P</jats:italic> = 0.027) were correlated with early recurrence. In the subgroup of patients with AFP &lt;200 ng/mL, high <jats:italic toggle="yes">MTA1dE4</jats:italic>, but not total <jats:italic toggle="yes">MTA1</jats:italic>, expression could help predict early recurrence (<jats:italic toggle="yes">P</jats:italic> = 0.0195). <jats:italic toggle="yes">In vitro</jats:italic>, 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. <jats:italic toggle="yes">Conclusion</jats:italic>: <jats:italic toggle="yes">MTA1dE4</jats:italic> 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.</jats:p>
  • Access State: Open Access