Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.
Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.
Hepatology. 2019 Jul;70(1):184-197. doi: 10.1002/hep.30581. Epub 2019 Apr 14.
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.
转移性肿瘤抗原 1（MTA1）的过表达与乙型肝炎病毒（HBV）相关的肝细胞癌（HBV-HCC）的预后不良相关。本研究旨在检测 MTA1 及其外显子 4 缺失形式（MTA1dE4）（MTA1 的最丰富剪接变体）在接受 HBV-HCC 根治性切除的患者中的表达的临床意义。我们回顾性收集了 102 例 HBV-HCC 患者，并接受了根治性切除，通过 RT-qPCR 检测其配对的非肿瘤和肿瘤肝组织中总 MTA1/MTA1dE4 的表达水平。分析 MTA1/MTA1dE4 表达与各种肿瘤特征以及肿瘤复发之间的关系。在中位随访 4 年期间，25 例患者（24.5%）表现为早期复发（切除后 12 个月内），42 例（54.5%）表现为晚期复发。在 Kaplan-Meier 分析中，肿瘤中 MTA1dE4 的过表达与早期复发相关（P = 0.0365），但与晚期复发无关。在多变量分析中，只有甲胎蛋白（AFP）≥200ng/ml（P = 0.006）和大肿瘤直径（P = 0.027）与早期复发相关。在 AFP<200ng/ml 的患者亚组中，高 MTA1dE4 表达，而不是总 MTA1 表达，有助于预测早期复发（P = 0.0195）。在体外，进行 HCC 细胞的划痕愈合和侵袭实验，发现 MTA1dE4 在外显子 4 缺失形式下表现出比全长 MTA1 更高的促进肝癌细胞迁移和侵袭的能力。结论：MTA1dE4 表达与侵袭性更强的肿瘤特征相关，可能作为预测 HBV-HCC 早期复发的更敏感标志物，尤其是在 AFP 较低的患者中。
