Prognostic Significance of p53, mTOR, c-Met, IGF-1R, and HSP70 Overexpression after the Resection of Hepatocellular Carcinoma
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Background/Aims: The current study examines the expression of molecular biomarkers in hepatocellular carcinoma (HCC) and whether these findings correlate with the clinicopathologic features of the disease and patient survival. Methods: We analyzed the immunohistochemical expression of p53, mammalian target of rapamycin (mTOR), c-Met, and insulin-like growth factor 1 receptor (IGF-1R) heat shock protein 70 (HSP70) with the clinicopathologic features of 83 HCCs. Results: p53 expression was higher in the male patients with undifferentiated histological tumor grades, cirrhosis, and portal vein invasion. High 48 c-Met expression correlated with cirrhosis, and high mTOR expression correlated with the tumor grade and cirrhosis. High IGF-1R expression correlated with the tumor grade and cirrhosis. A multivariate analysis identified a significant relationship between the high expression of p53, tumor grade, and portal vein invasion. In addition, a high expression of mTOR was related to tumor grade and cirrhosis, and a high expression of HSP70 was related to portal vein invasion in a multivariate analysis. The Kaplan-Meier survival curve for patients with high versus low Edmondson grades and p53 expression was statistically significant. Conclusions: p53, mTOR, and IGF-1R expression correlated with the Edmondson tumor grade in a univariate analysis, while p53 and mTOR correlated with the Edmondson tumor grade in a multivariate analysis. In addition, the tumor grade was found to predict survival. p53 was primarily related to the clinicopathologic features compared to other markers, and it is a poor prognostic factor of survival.
Abstract
Background/Aims: The current study examines the expression of molecular biomarkers in hepatocellular carcinoma (HCC) and whether these findings correlate with the clinicopathologic features of the disease and patient survival. Methods: We analyzed the immunohistochemical expression of p53, mammalian target of rapamycin (mTOR), c-Met, and insulin-like growth factor 1 receptor (IGF-1R) heat shock protein 70 (HSP70) with the clinicopathologic features of 83 HCCs. Results: p53 expression was higher in the male patients with undifferentiated histological tumor grades, cirrhosis, and portal vein invasion. High 48 c-Met expression correlated with cirrhosis, and high mTOR expression correlated with the tumor grade and cirrhosis. High IGF-1R expression correlated with the tumor grade and cirrhosis. A multivariate analysis identified a significant relationship between the high expression of p53, tumor grade, and portal vein invasion. In addition, a high expression of mTOR was related to tumor grade and cirrhosis, and a high expression of HSP70 was related to portal vein invasion in a multivariate analysis. The Kaplan-Meier survival curve for patients with high versus low Edmondson grades and p53 expression was statistically significant. Conclusions: p53, mTOR, and IGF-1R expression correlated with the Edmondson tumor grade in a univariate analysis, while p53 and mTOR correlated with the Edmondson tumor grade in a multivariate analysis. In addition, the tumor grade was found to predict survival. p53 was primarily related to the clinicopathologic features compared to other markers, and it is a poor prognostic factor of survival.
참고문헌 (28)
- Farazi PA, "Hepatocellular carcinoma pathogenesis: from genes to environment", Nat Rev Cancer, 6, pp.674~687 (2006)
- Tabor E, "Tumor suppressor genes, growth factor genes, and oncogenes in hepatitis B virus-associated hepatocellular carcinoma", J Med Virol, 42, pp.357~365 (1994)
- Rogler CE, "Cellular and molecular mechanisms of hepatocarcinogenesis", Semin Liver Dis, 12, pp.265~278 (1992)
- 성창옥, "간세포암종의 간절제술 후 p53 과발현의 예후에 미치는 영향", 대한소화기학회지, 45(6), pp.425~430 (2005), 대한소화기학회
- Pang RW, "From molecular biology to targeted therapies for hepatocellular carcinoma: the future is now", Oncology, 72(Suppl 1:), pp.30~44 (2007)
- Llovet JM, "Molecular targeted therapies in hepatocellular carcinoma", Hepatology, 48, pp.1312~1327 (2008)
- Edmondson HA, "Primary carcinoma of the liver: a study of 100 cases among 48,900 necropsies", Cancer, 7, pp.462~503 (1954)
- Hoos A, "Tissue microarray profiling of cancer specimens and cell lines: opportunities and limitations", Lab Invest, 81, pp.1331~1338 (2001)
- Greenblatt MS, "Mutations in the p53 tumor suppressor gene: clues to cancer etiology and molecular pathogenesis", Cancer Res, 54, pp.4855~4878 (1994)
- Osada S, "Clinical significance of combination study of apoptotic factors and proliferating cell nuclear antigen in estimating the prognosis of hepatocellular carcinoma", J Surg Oncol, 85, pp.48~54 (2004)
- Fujimoto Y, "Alterations of tumor suppressor genes and allelic losses in human hepatocellular carcinomas in China", Cancer Res, 54, pp.281~285 (1994)
- Song TJ, "Comparison of hepatocellular carcinoma in American and Asian patients by tissue array analysis", J Surg Oncol, 106, pp.84~88 (2012)
- Staib F, "TP53 and liver carcinogenesis", Hum Mutat, 21, pp.201~216 (2003)
- Buendia MA., "Genetics of hepatocellular carcinoma", Semin Cancer Biol, 10, pp.185~200 (2000)
- Ng IO, "Overexpression of p53 in hepatocellular carcinomas: a clinicopathological and prognostic correlation", J Gastroenterol Hepatol, 10, pp.250~255 (1995)
- Jeng KS, "Is the p53 gene mutation of prognostic value in hepatocellular carcinoma after resection?", Arch Surg, 135, pp.1329~1333 (2000)
- Nishida N, "Role and mutational heterogeneity of the p53 gene in hepatocellular carcinoma", Cancer Res, 53, pp.368~372 (1993)
- Fausto N, "Liver regeneration", Hepatology, 43(2 Suppl 1), pp.S45~S53 (2006)
- Comoglio PM, "Drug development of MET inhibitors: targeting oncogene addiction and expedience", Nat Rev Drug Discov, 7, pp.504~516 (2008)
- Bjornsti MA, "The TOR pathway: a target for cancer therapy", Nat Rev Cancer, 4, pp.335~348 (2004)
- Schmitz KJ, "Activation of the ERK and AKT signalling pathway predicts poor prognosis in hepatocellular carcinoma and ERK activation in cancer tissue is associated with hepatitis C virus infection", J Hepatol, 48, pp.83~90 (2008)
- Pollak MN, "Insulin-like growth factors and neoplasia", Nat Rev Cancer, 4, pp.505~518 (2004)
- Scharf JG, "The role of the IGF axis in hepatocarcinogenesis", Horm Metab Res, 35, pp.685~693 (2003)
- Didelot C, "Heat shock proteins: endogenous modulators of apoptotic cell death", Handb Exp Pharmacol, (172), pp.171~198 (2006)
- Chuma M, "Expression profiling in multistage hepatocarcinogenesis: identification of HSP70 as a molecular marker of early hepatocellular carcinoma", Hepatology, 37, pp.198~207 (2003)
- Haratake J, "Predictable factors for estimating prognosis of patients after resection of hepatocellular carcinoma", Cancer, 72, pp.1178~1183 (1993)
- Lauwers GY, "Prognostic histologic indicators of curatively resected hepatocellular carcinomas: a multi-institutional analysis of 425 patients with definition of a histologic prognostic index", Am J Surg Pathol, 26, pp.25~34 (2002)
- Lai CL, "Histologic prognostic indicators in hepatocellular carcinoma", Cancer, 44, pp.1677~1683 (1979)
