An Jihyun, Na Seong Kyun, Shim Ju Hyun, Park Yang Soon, Jun Mi Jung, Lee Joo Ho, Song Gi-Won, Lee Hac Chu, Yu Eunsil
Department of Gastroenterology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Department of Internal Medicine, Jeju National University Hospital, Jeju National University School of Medicine, Jeju, Korea.
J Surg Oncol. 2018 Apr;117(5):892-901. doi: 10.1002/jso.24994. Epub 2018 Feb 15.
Deregulation of methionine adenosyltransferase (MAT) is involved in hepatocarcinogenesis. This study aimed to investigate the prognostic implications of the level of histological MAT1A and MAT2A in patients with resected hepatocellular carcinoma (HCC).
A total of 210 patients with HCC who underwent curative resection between 2004 and 2011 were included. The levels of MAT proteins were immunohistochemically measured.
MAT1A and MAT2A were over-expressed in 134 (63.8%) and 124 (59.1%) of the 210 tumor tissues, respectively. Up-regulation of tumoral MAT1A was independently associated with male gender, and inversely related to tumors >5 cm (adjusted odds ratios [OR] 2.59, P = 0.008, and OR 0.44, P = 0.012, respectively). Enhanced MAT2A expression was significantly related to age ≥60 years and serum AFP >200 ng/mL (OR 0.51, P = 0.030; and OR 2.65, P = 0.003; respectively). Tumoral MAT2A over-expression independently predicted an increased rate of recurrence within 1 year after hepatectomy (adjusted hazard ratio [HR] 2.45, P = 0.012), but that was not the case for MAT1A expression (HR 0.90, P = 0.744). High MAT2A was also an independent predictor of early recurrence (HR 2.54, P = 0.034) in the subset of patients without microvascular invasion (n = 155).
Over-expression of MAT2A in HCC may be a useful biomarker for predicting and monitoring tumor recurrence, especially early after hepatic resection.
蛋氨酸腺苷转移酶（MAT）失调参与肝癌发生。本研究旨在探讨组织学上MAT1A和MAT2A水平对肝细胞癌（HCC）切除患者的预后意义。
纳入2004年至2011年间接受根治性切除的210例HCC患者。采用免疫组织化学方法检测MAT蛋白水平。
210例肿瘤组织中，MAT1A和MAT2A分别在134例（63.8%）和124例（59.1%）中过表达。肿瘤MAT1A上调与男性性别独立相关，与肿瘤>5 cm呈负相关（校正比值比[OR]分别为2.59，P = 0.008；OR 0.44，P = 0.012）。MAT2A表达增强与年龄≥60岁和血清甲胎蛋白>200 ng/mL显著相关（OR分别为0.51，P = 0.030；OR 2.65，P = 0.003）。肿瘤MAT2A过表达独立预测肝切除术后1年内复发率增加（校正风险比[HR] 2.45，P = 0.012），但MAT1A表达情况并非如此（HR 0.90，P = 0.744）。在无微血管侵犯的患者亚组（n = 155）中，高MAT2A也是早期复发的独立预测因子（HR 2.54，P = 0.034）。
HCC中MAT2A过表达可能是预测和监测肿瘤复发的有用生物标志物，尤其是肝切除术后早期。
