Expressions and significance of gp96 and Mcl-1 in liver cirrhosis and hepatocellular carcinoma tissues

doi:10.3969/j.issn.1673-8640.2015.02.020

Abstract

Abstract: Objective

To investigate the expressions and clinical pathological significance of gp96 and myeloid cell leukemia-1(Mcl-1) in liver cirrhosis and hepatocellular carcinoma tissues to study preliminarily their relationships with the genesis and progression development of liver cirrhosis and hepatocellular carcinoma.

Methods

The expressions of gp96 and Mcl-1 were detected respectively by ENVISION immunohistochemistry in 19 liver cirrhosis tissues (liver cirrhosis tissues beside hepatocellular carcinoma), 32 hepatocellular carcinoma tissues and 21 control tissues (non-liver cirrhosis tissues beside hepatocellular carcinoma). Their relationships of expressions with clinical pathological characteristics of hepatocellular carcinoma were investigated. The expressions of gp96 and Mcl-1 of liver cirrhosis tissues beside hepatocellular carcinoma, hepatocellular carcinoma tissues and non-liver cirrhosis tissues beside hepatocellular carcinoma from one patient were detected, and the positive expression rates were compared.

Results

The positive expression rate of gp96 increased gradually from control, liver cirrhosis to hepatocellular carcinoma groups, which showed significantly different (P<0.05). The positive expression of gp96 had relationships with tumor envelope and TNM staging(P<0.05), and there was no relationship with sex, age, tumor size, serum alpha-fetoprotein (AFP), histological grading and clinical staging (P>0.05). Mcl-1 positive expression in hepatocellular carcinoma and liver cirrhosis groups markedly increased compared to control group, respectively(P<0.05), and there was no statistical significance between liver cirrhosis and hepatocellular carcinoma groups (P>0.05). The positive expression of Mcl-1 had relationships with tumor necrosis and TNM staging(P<0.05). The positive expression rate of gp96 in hepatocellular carcinoma group was significantly higher than those in liver cirrhosis and control groups (P<0.05). The positive expression rate of Mcl-1 in hepatocellular carcinoma group was higher than that in control group, and had no statistical significance with that in liver cirrhosis group (P>0.05).

Conclusions

The overexpressions of gp96 and Mcl-1 are related to the genesis and progression of hepatocellular carcinoma. The gp96 may implicate in the formation and development of liver cirrhosis as well as its subsequent malignant transformation, and may be used as a prognostic biomarker for hepatocellular carcinoma.

Key words: gp96, Myeloid cell leukemia sequence-1, Hepatocellular carcinoma, Liver cirrhosis

CLC Number:

R446.1

LI Feng, WEI Qun, HUANG Dongfeng, ZHANG Hon. Expressions and significance of gp96 and Mcl-1 in liver cirrhosis and hepatocellular carcinoma tissues[J]. Laboratory Medicine, 2015, 30(2): 185-190.

Figures/Tables 7

References 20

[1]	PARKIN DM,BRAY F,FERLAY J,et al.Global cancer statistics, 2002[J]. CA Cancer J Clin,2005,55(2):74-108.
[2]	YANG L,PARKIN DM,FERLAY J,et al.Estimates of cancer incidence in China for 2000 and projections for 2005[J]. Cancer Epidemiol Biolmarkers Prev,2005,14(1):243-250.
[3]	LUO RH,ZHAO ZX,ZHOU XY,et al.Risk factors for primary liver carcinoma in Chinese population[J]. World J Gastroenterol,2005,11(28):4431-4434.
[4]	HUA Y, WHITE-GILBERTSON S, KELLNER J, et al.Molecular chaperone gp96 is a novel therapeutic target of multiple myeloma[J]. Clin Cancer Res,2013,19(22):6242-6251.
[5]	SANO M, NAKANISHI Y, YAGASAKI H, et al.Overexpression of anti-apoptotic Mcl-1 in testicular germ cell tumours[J]. Histopathology,2005,46(5):532-539.
[6]	邢传平,刘斌,董亮. 免疫组织化学标记结果的判断方法[J].中华病理学杂志,2001,30(4):318.
[7]	FU Y,LEE AS.Glucose regulated proteins in cancer progression,drug resistance and immunotherapy[J]. Cancer Biol Ther,2006,5(7):741-744.
[8]	WANG Q,HE Z,ZHANG J,et al.Overexpression of endoplasmic reticulum molecular chaperone GRP94 and GRP78 in human lung cancer tissues and its significance[J]. Cancer Detect Prev,2005,29(6):544-551.
[9]	SINGH-JASUJA H,SCHERER HU,HILF N,et al.The heat shock protein gp96 induces maturation of dendritic cells and down-regulation of its receptor[J]. Eur J Immunol,2000, 30(8):2211-2215.
[10]	BELLI F,TESTORI A,RIVOLTINI L,et al.Vaccination of metastatic melanoma patients with autologous tumor-derived heat shock protein gp96-peptide complexes: clinical and immunologic findings[J]. J Clin Oncol,2002,20(20):4169-4180.
[11]	MAZZAFERRO V,COPPA J,CARRABBA MG,et al.Vaccination with autologous tumor-derived heat-shock protein gp96 after liver resection for metastatic colorectal cancer[J]. Clin Cancer Res,2003,9(9):3235-3245.
[12]	XU Z,JENSEN G,YEN TS.Activation of hepatitis B virus S promoter by the viral large surface protein via induction of stress in the endoplasmic reticulum[J]. J Virol,1997,71(10):7387-7392.
[13]	KIM YS,LIM HK,RHIM H,et al.Recurrence of hepatocellular carcinoma after liver transplantation: patterns and prognostic factors based on clinical and radiologic features[J]. AJR AM J Roentgenol,2007,189(2):352-358.
[14]	LIU H,PENG HW,CHENG YS,et al.Stabilization and enhancement of the antiapoptotic activity of mcl-1 by TCTP[J]. Mol Cell Biol,2005, 25(8):3117-3126.
[15]	SONG L,COPPOLA D,LIVINGSTON S,et al.Mcl-1 regulates survival and sensitivity to diverse apoptotic stimuli in human non-small cell lung cancer cells[J]. Cancer Biol Ther,2005,4(3):267-276.
[16]	CHUNG TK,CHEUNG TH,LO WK,et al.Expression of apoptotic regulators and their significance in cervical cancer[J]. Cancer Lett,2002,180(1):63-68.
[17]	FLEISCHER B,SCHULZE-BERGKAMEN H,SCHUCHMANN M,et al.Mcl-1 is an anti-apoptotic factor for human hepatocellular carcinoma[J]. Int J Oncol,2006,28(1):25-32.
[18]	SIEGHART W,LOSERT D,STROMMER S,et al.Mcl-1 overexpression in hepatocellular carcinoma: a potential target for antisense therapy[J]. J Hepatol,2006,44(1):151-157.
[19]	CRAIG RW.MCL1 provides a window on the role of the BCL2 family in cell proliferation,differentiation and tumorigenesis[J]. Leukemia,2002,16(4):444-454.
[20]	EDWARDS SW, DEROUET M, HOWSE M, et al.Regulation of neutrophil apoptosis by Mcl-1[J]. Biochem Soc Trans,2004,32(Pt3):489-492.

组别	例数	gp96		Mcl-1
肝癌组	32	27	(84.38)^*#	14	(43.75)^*
肝硬化组	19	10	(52.63)^*	6	(31.58)^*
对照组	21	2	(9.52)	1	(4.76)

组别	例数	gp96		Mcl-1
肝癌组	32	27	(84.38)^*#	14	(43.75)^*
肝硬化组	19	10	(52.63)^*	6	(31.58)^*
对照组	21	2	(9.52)	1	(4.76)

组别	例数	gp96	Mcl-1
肝癌组	19	16(84.21)	9(47.37)
配对癌旁肝硬化组	19	10(52.63)^*	6(31.58)

组别	例数	gp96	Mcl-1
肝癌组	19	16(84.21)	9(47.37)
配对癌旁肝硬化组	19	10(52.63)^*	6(31.58)

组别	例数	gp96	Mcl-1
肝癌组	13	11(84.62)	6	(46.15)
配对癌旁非肝硬化组	13	2(15.38)^*	1	(7.69)^*