Abstract:Objective To investigate the expression and clinical significance of Jagged-1 protein in hepatitis B virus(HBV)-related hepatocellular carcinoma. Methods Between November 2008 and June 2012,a total of 110 adult patients with HBV-related HCC undergoing hepatectomy in our center were enrolled and tissue microarrays were used to detect the level of Jagged-1 expression before retrospective analysis was made to investigate the relationships between Jagged-1 expression and the clinical characteristics and prognosis.Results The Results of tissue microarrays showed that the rate of Jagged-1 over-expression was significantly higher in HCC tissues(44.5%) than that in paired nocancerous tissues(22.3%;χ2=12.16,P<0.0001).Over-expression of Jagged-1 protein was significantly correlated with microvascular invasion in HCC samples. Kaplan-Meier survival analysis in both cohorts showed that patients with over-expression of Jagged-1 had lower 1, 3, 5-year overall survival rate (87.5%, 64.1%, 46.5% vs 96.7%, 84.5%, 66.9%in over- or low-expression groups,P=0.0139) .Conclusions Increased Jagged-1 expression levels are closely associated with microvascular invasion and poor prognosis for HBV-related HCC patients.
Forner A, Llovet J M, Bruix J. Hepatocellular carcinoma [J]. Lancet, 2012, 379(9822): 1245-1255.
[2]
Chen W,Zheng R,Baade P D,et al.Cancer statistics in China, 2015[J].CA Cancer J Clin,2016,66(2):115-132.
[3]
Bruix J, Sherman M, American Assocition For The Study of Liver D. Management of hepatocellular carcinoma: an update [J]. Hepatology, 2011, 53(3): 1020-1022.
[4]
Poon R T. Prevention of recurrence after resection of hepatocellular carcinoma: a daunting challenge [J]. Hepatology, 2011, 54(3): 757-759.
[5]
Andersson E R, Sandberg R, Lendahl U. Notch signaling: simplicity in design, versatility in function [J]. Development, 2011, 138(17): 3593-3612.
[6]
Gil-Garcia B, Baladron V. The complex role of NOTCH receptors and their ligands in the development of hepatoblastoma, cholangiocarcinoma and hepatocellular carcinoma [J]. Biol Cell, 2016, 108(2): 29-40.
[7]
Tschaharganeh D F, Chen X, Latzko P, et al. Yes-associated protein up-regulates Jagged-1 and activates the Notch pathway in human hepatocellular carcinoma [J]. Gastroenterology, 2013, 144(7): 1530-1542.
[8]
Hori K, Sen A, Artavanis-Tsakonas S. Notch signaling at a glance [J]. J Cell Sci, 2013, 126(Pt 10): 2135-2140.
[9]
Geisler F, STtrazzabosco M. Emerging roles of Notch signaling in liver disease [J]. Hepatology, 2015, 61(1): 382-392.
[10]
Viatour P, Ehmer U, Saddic L A, et al. Notch signaling inhibits hepatocellular carcinoma following inactivation of the RB pathway [J]. J Exp Med, 2011, 208(10): 1963-1976.
[11]
Gao J, Xiong Y, Wang Y, et al. Hepatitis B virus X protein activates Notch signaling by its effects on Notch1 and Notch4 in human hepatocellular carcinoma [J]. Int J Oncol, 2016, 48(1): 329-337.
[12]
Greenhill C. Liver cancer: different effects of the Notch receptors in liver cancer revealed [J]. Nat Rev Gastroenterol Hepatol, 2014, 11(12): 703.
[13]
Razumilava N, Gores G J. Notch-driven carcinogenesis: the merging of hepatocellular cancer and cholangiocarcinoma into a common molecular liver cancer subtype [J]. J Hepatol, 2013, 58(6): 1244-1245.
[14]
Goessling W. Deciphering hepatocellular carcinoma: from bench to bedside and back [J]. Gastroenterology, 2009, 137(3): 786-788.
[15]
Dupont Bierre E, Compagnon P, Raoul J L, et al. Resection of hepatocellular carcinoma in noncirrhotic liver: analysis of risk factors for survival [J]. J Am Coll Surg, 2005, 201(5): 663-670.
[16]
Mccright B, Lozier J, Gridley T. A mouse model of Alagille syndrome: Notch2 as a genetic modifier of Jag1 haploinsufficiency [J]. Development, 2002, 129(4): 1075-1082.
[17]
Morell C M, Strazzabosco M. Notch signaling and new therapeutic options in liver disease [J]. J Hepatol, 2014, 60(4): 885-890.