Jihyun An1, Seong Kyun Na1,2, Ju Hyun Shim1, Yang Soon Park3, Mi Jung Jun1, Joo Ho Lee1,4, Gi-Won Song5, Hac Chu Lee1, Eunsil Yu3. 1. Department of Gastroenterology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. 2. Department of Internal Medicine, Jeju National University Hospital, Jeju National University School of Medicine, Jeju, Korea. 3. Department of Pathology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. 4. Department of Internal Medicine, Division of Gastroenterology and Hepatology, CHA Bundang Medical Center, CHA University, Seongnam, Korea. 5. Division of Liver Transplantation and Hepatobiliary Surgery, Department of Surgery, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Abstract
BACKGROUND AND OBJECTIVES: 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). METHODS: 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. RESULTS: 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). CONCLUSIONS: Over-expression of MAT2A in HCC may be a useful biomarker for predicting and monitoring tumor recurrence, especially early after hepatic resection.
BACKGROUND AND OBJECTIVES: 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). METHODS: 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. RESULTS: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). CONCLUSIONS: Over-expression of MAT2A in HCC may be a useful biomarker for predicting and monitoring tumor recurrence, especially early after hepatic resection.