Metadherin Is a Prognostic Predictor of Hepatocellular Carcinoma after Curative Hepatectomy
2
조회
0
다운로드
6
인용
0
참고문헌
키워드
초록
Background/Aims: The prognosis after surgical resection of hepatocellular carcinoma (HCC) remains poor because of a high rate of recurrence. Thus, it is crucial to identify patients with a high risk of recurrence after curative hepatectomy and to develop more effective and targeted treatment strategies to improve disease outcomes. In this study, we investigated the roles of metadherin (MTDH) in the prognosis of HCC. Methods: We investigated MTDH expression using immunohistochemistry in tumor tissue microarrays of 288 primary HCC patients who underwent curative surgical resection. Results: High MTDH expression was observed in 138 of the 288 HCC cases (47.9%). High MTDH expression was associated with a younger age (p<0.001), higher Edmondson grade (p<0.001), microvascular invasion (p<0.001), higher American Joint Committee on Cancer T stage (p=0.001),and higher α-fetoprotein level (p=0.003). Multivariate analyses revealed that high MTDH expression (p=0.014), higher Barcelona-Clinic Liver Cancer (BCLC) stage (p<0.001), and Edmondson grade III (p=0.042) were independent predictors of shorter disease-free survival (DFS). Higher BCLC stage (p<0.001) and Edmondson grade III (p=0.047) were also independent predictors of shorter disease-specific survival. Conclusions: High MTDH expression may be a prognostic predictor of shorter DFS in HCC patients after curative hepatectomy.
Abstract
Background/Aims: The prognosis after surgical resection of hepatocellular carcinoma (HCC) remains poor because of a high rate of recurrence. Thus, it is crucial to identify patients with a high risk of recurrence after curative hepatectomy and to develop more effective and targeted treatment strategies to improve disease outcomes. In this study, we investigated the roles of metadherin (MTDH) in the prognosis of HCC. Methods: We investigated MTDH expression using immunohistochemistry in tumor tissue microarrays of 288 primary HCC patients who underwent curative surgical resection. Results: High MTDH expression was observed in 138 of the 288 HCC cases (47.9%). High MTDH expression was associated with a younger age (p<0.001), higher Edmondson grade (p<0.001), microvascular invasion (p<0.001), higher American Joint Committee on Cancer T stage (p=0.001),and higher α-fetoprotein level (p=0.003). Multivariate analyses revealed that high MTDH expression (p=0.014), higher Barcelona-Clinic Liver Cancer (BCLC) stage (p<0.001), and Edmondson grade III (p=0.042) were independent predictors of shorter disease-free survival (DFS). Higher BCLC stage (p<0.001) and Edmondson grade III (p=0.047) were also independent predictors of shorter disease-specific survival. Conclusions: High MTDH expression may be a prognostic predictor of shorter DFS in HCC patients after curative hepatectomy.
참고문헌 (22)
- El-Serag HB, "Hepatocellular carcinoma: epidemiology and molecular carcinogenesis", Gastroenterology, 132, pp.2557~2576 (2007)
- Llovet JM, "Resection and liver transplantation for hepatocellular carcinoma", Semin Liver Dis, 25, pp.181~200 (2005)
- Poon RT, "Prevention of recurrence after resection of hepatocellular carcinoma: a daunting challenge", Hepatology, 54, pp.757~759 (2011)
- Ho MC, "A gene expression profile for vascular invasion can predict the recurrence after resection of hepatocellular carcinoma: a microarray approach", Ann Surg Oncol, 13, pp.1474~1484 (2006)
- Kang DC, "Cloning and characterization of HIV-1-inducible astrocyte elevated gene-1, AEG-1", Gene, 353, pp.8~15 (2005)
- Hu G, "The multifaceted role of MTDH", AEG-1 in cancer progression, 2009, pp.15, 5615~5620
- Hu G, "MTDH activation by 8q22 genomic gain promotes chemoresistance and metastasis of poor-prognosis breast cancer", Cancer Cell, 15, pp.9~20 (2009)
- Emdad L, "Activation of the nuclear factor kappaB pathway by astrocyte elevated gene-1: implications for tumor progression and metastasis", Cancer Res, 66, pp.1509~1516 (2006)
- Yoo BK, "Astrocyte elevated gene-1 regulates hepatocellular carcinoma development and progression", J Clin Invest, 119, pp.465~477 (2009)
- "Astrocyte elevated gene-1 activates cell survival pathways through PI3K-Akt signaling", ONCOGENE, 27(8), pp.1114~1121 (2008), NATURE PUBLISHING GROUP
- Kikuno N, "Knockdown of astrocyte-elevated gene-1 inhibits prostate cancer progression through upregulation of FOXO3a activity", Oncogene, 26, pp.7647~7655 (2007)
- Brown DM, "Metadherin, a cell surface protein in breast tumors that mediates lung metastasis", Cancer Cell, 5, pp.365~374 (2004)
- Yu C, "Overexpression of astrocyte elevated gene-1 (AEG-1) is associated with esophageal squamous cell carcinoma (ESCC) progression and pathogenesis", Carcinogenesis, 30, pp.894~901 (2009)
- Song H, "Prognostic significance of AEG-1 expression in colorectal carcinoma", Int J Colorectal Dis, 25, pp.1201~1209 (2010)
- Zhu K, "Metadherin promotes hepatocellular carcinoma metastasis through induction of epithelial-mesenchymal transition", Clin Cancer Res, 17, pp.7294~7302 (2011)
- Gong Z, "Prognostic significance of metadherin overexpression in hepatitis B virus-related hepatocellular carcinoma", Oncol Rep, 27, pp.2073~2079 (2012)
- Edmondson HA, "Primary carcinoma of the liver: a study of 100 cases among 48,900 necropsies", Cancer, 7, pp.462~503 (1954)
- Liver Cancer Study Group of Japan, "General rules for the clinical and pathological study of primary liver cancer. 2nd ed" (2003), Kanehara
- Hoshida Y, "Gene expression in fixed tissues and outcome in hepatocellular carcinoma", N Engl J Med, 359, pp.1995~2004 (2008)
- International Working Party, "Terminology of nodular hepatocellular lesions", Hepatology, 22, pp.983~993 (1995)
- Edge SB, "AJCC cancer staging manual. 7th ed" (2010), Springer
- Llovet JM, "Prognosis of hepatocellular carcinoma: the BCLC staging classification", Semin Liver Dis, 19, pp.329~338 (1999)