联合检测血清GP73和AFP对原发性肝癌诊断的临床价值
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摘要
目的
探讨血清高尔基体糖蛋白(GP73)对原发性肝癌(primary liver carcinoma PLC)(以下简称肝癌)的诊断价值及分析GP73和甲胎蛋白(AFP)联合检测对PLC诊断的临床意义,为PLC诊断提供一种新的有效检测手段。
方法
采用双抗体夹心酶联免疫定量测定方法检测144例PLC患者、50例肝硬化患者、100例乙型肝炎患者、50例其他恶性肿瘤患者、26例肝良性病变患者、84例HBV携带者和50例正常人对照组的血清GP73浓度。采用临床电化学发光法测定血清AFP作为参比。
结果
1.PLC组血清GP73水平与肝硬化组、乙型肝炎组、HBV携带者组、其他恶性肿瘤组、肝良性病变组和正常人对照组的血清GP73水平相比显著增高(168.22±1045.58vs149.81±1091.98、30.32±146.73、19.65±137.3930.05±147.35、28.58±143.27和13.98±8.74,P=0.041、0.000、0.000、0.000、0.000和0.000)。通过受试者工作特征(receiver operating characteristic, ROC)曲线设定GP73水平,GP73为64ng/mL作为诊断PLC的临界值切点(cut-off)时,GP73诊断PLC的敏感度和特异度达到最佳,分别为83.3%和88.3%。
2.在PLC组,GP73诊断PLC的敏感度与AFP比较有统计学差异(83.3%vs72.2%,P=0.023),GP73诊断PLC的敏感度要高于AFP。
3.联合检测血清GP73和AFP,诊断PLC的敏感度提高到94.4%,特异度为65.5%,敏感度显著高于GP73(83.3%)或AFP(72.2%)单项检测。
结论
1.GP73是一种敏感度更高、特异度更好的新的肝癌标志物,检测血清GP73水平对PLC诊断有较好的敏感度和特异度,均优于AFP。
2.联合检测血清GP73和AFP可有效减少AFP阴性或低浓度肝癌的漏诊率,提高肝癌的检出率和诊断肝癌的准确性,是更有效的诊断肝癌的肿瘤标志物组合。
OBJECTIVES
To explore the diagnostic value of serum GP73in the patient of primary liver carcinoma (PLC), discuss the diagnostic value of the joint roles of serum GP73and AFP in the diagnosis of PLC, and provide a new detection method for the diagnosis of PLC.
METHODS
ELISA method was used to detect the serum level of GP73in144cases of PLC,50cases of hepatic cirrhosis,100cases of hepatitis,50cases of other malignant tumors,26cases of liver benign lesions,84cases of hepatitis carriers and50cases of healthy volunteers (as the controls). The electrochemical luminescence method was used to detect the serum level of AFP of the all, and the level of AFP was as a comparison.
RESULTS
1. The level of serum AFP and GP73in the group of PLC were significantly higher than that of hepatic cirrhosis, hepatitis, other malignant tumors, liver benign lesions, hepatitis carriers and healthy volunteers (as the controls)(168.22±1045.58vs149.81±1091.98、30.32±146.73、19.65±137.39、 30.05±147.35、28.58±143.27和13.98±8.74,P=0.041、0.000、0.000、0.000、0.000和0.000), the critical value for GP73was determined to be64.4ng/mL through the ROC curves, under the critical value the sensitivity and specificity of the GP73was83.3%and88.3%, and these were the best.
2. The difference of GP73and AFP in the group of PLC was statistically significant (83.3%vs72.2%, P=0.023).
3. The diagnostic sensitivity of the joint roles of serum GP73and AFP was increased to94.4%, and the specificity up to65.5%. The Sensitivity of the joint roles of the both was significantly higher than one single detection of GP73(83.3%) or AFP (72.2%).
CONCLUSION
1. The GP73was one of the best liver tumor markers, which had better sensitivity and specificity than AFP. The diagnostic sensitivity and specificity of the serum GP73in the diagnosis of PLC was better than AFP.
2. The joint roles of serum GP73and AFP could reduce effectively the missed diagnosis and of PLC whose AFP was negative or low concentration, it could improve the detection rate and the diagnosis accuracy of PLC, it was one of the best effective diagnosis combination in tumor markers of PLC.
探讨血清高尔基体糖蛋白(GP73)对原发性肝癌(primary liver carcinoma PLC)(以下简称肝癌)的诊断价值及分析GP73和甲胎蛋白(AFP)联合检测对PLC诊断的临床意义,为PLC诊断提供一种新的有效检测手段。
方法
采用双抗体夹心酶联免疫定量测定方法检测144例PLC患者、50例肝硬化患者、100例乙型肝炎患者、50例其他恶性肿瘤患者、26例肝良性病变患者、84例HBV携带者和50例正常人对照组的血清GP73浓度。采用临床电化学发光法测定血清AFP作为参比。
结果
1.PLC组血清GP73水平与肝硬化组、乙型肝炎组、HBV携带者组、其他恶性肿瘤组、肝良性病变组和正常人对照组的血清GP73水平相比显著增高(168.22±1045.58vs149.81±1091.98、30.32±146.73、19.65±137.3930.05±147.35、28.58±143.27和13.98±8.74,P=0.041、0.000、0.000、0.000、0.000和0.000)。通过受试者工作特征(receiver operating characteristic, ROC)曲线设定GP73水平,GP73为64ng/mL作为诊断PLC的临界值切点(cut-off)时,GP73诊断PLC的敏感度和特异度达到最佳,分别为83.3%和88.3%。
2.在PLC组,GP73诊断PLC的敏感度与AFP比较有统计学差异(83.3%vs72.2%,P=0.023),GP73诊断PLC的敏感度要高于AFP。
3.联合检测血清GP73和AFP,诊断PLC的敏感度提高到94.4%,特异度为65.5%,敏感度显著高于GP73(83.3%)或AFP(72.2%)单项检测。
结论
1.GP73是一种敏感度更高、特异度更好的新的肝癌标志物,检测血清GP73水平对PLC诊断有较好的敏感度和特异度,均优于AFP。
2.联合检测血清GP73和AFP可有效减少AFP阴性或低浓度肝癌的漏诊率,提高肝癌的检出率和诊断肝癌的准确性,是更有效的诊断肝癌的肿瘤标志物组合。
OBJECTIVES
To explore the diagnostic value of serum GP73in the patient of primary liver carcinoma (PLC), discuss the diagnostic value of the joint roles of serum GP73and AFP in the diagnosis of PLC, and provide a new detection method for the diagnosis of PLC.
METHODS
ELISA method was used to detect the serum level of GP73in144cases of PLC,50cases of hepatic cirrhosis,100cases of hepatitis,50cases of other malignant tumors,26cases of liver benign lesions,84cases of hepatitis carriers and50cases of healthy volunteers (as the controls). The electrochemical luminescence method was used to detect the serum level of AFP of the all, and the level of AFP was as a comparison.
RESULTS
1. The level of serum AFP and GP73in the group of PLC were significantly higher than that of hepatic cirrhosis, hepatitis, other malignant tumors, liver benign lesions, hepatitis carriers and healthy volunteers (as the controls)(168.22±1045.58vs149.81±1091.98、30.32±146.73、19.65±137.39、 30.05±147.35、28.58±143.27和13.98±8.74,P=0.041、0.000、0.000、0.000、0.000和0.000), the critical value for GP73was determined to be64.4ng/mL through the ROC curves, under the critical value the sensitivity and specificity of the GP73was83.3%and88.3%, and these were the best.
2. The difference of GP73and AFP in the group of PLC was statistically significant (83.3%vs72.2%, P=0.023).
3. The diagnostic sensitivity of the joint roles of serum GP73and AFP was increased to94.4%, and the specificity up to65.5%. The Sensitivity of the joint roles of the both was significantly higher than one single detection of GP73(83.3%) or AFP (72.2%).
CONCLUSION
1. The GP73was one of the best liver tumor markers, which had better sensitivity and specificity than AFP. The diagnostic sensitivity and specificity of the serum GP73in the diagnosis of PLC was better than AFP.
2. The joint roles of serum GP73and AFP could reduce effectively the missed diagnosis and of PLC whose AFP was negative or low concentration, it could improve the detection rate and the diagnosis accuracy of PLC, it was one of the best effective diagnosis combination in tumor markers of PLC.
引文
[1]李谨峰,林川.血清肿瘤标志联合检测对原发性肝癌诊断价值的探讨[J].中华肿瘤防治杂志,2010,17(11)：877-879.
[2]Llovet JM, Burroughs A, Bruix J. Hepatocellular carcinoma. Lancet,2003, 362(9399):1907-1917. (PubMed)
[3]王树声,张振权,黄天壬,等.广西90年代初人口死亡原因抽样调查研究[J].广西预防医学,2005,11(3)：40-45.
[4]徐海峰,杨华瑜,张宏冰,等.改变肝癌早期诊断和治疗现状的新肝癌血清标志物.基础医学与临床,2008,28(1)：104-108.
[5]Marrero J, Romano P. GP73, a resident Golgi glyooprotein, is a novel serum marker for hepatocellular carcinoma. J Hepatol,2005,43(6):1007-1012.
[6]毛一雷,杨华瑜,徐海峰等.新的肝癌血清标记物GP73肝癌诊断中的初步研究.中华医学杂志,2008,88(14)：948-951.
[7]原发性肝癌诊疗规范(2011年版)[J].临床肿瘤学杂志,2011,(10)：929-946.
[8]中华医学会肝病学分会,中华医学会感染病学分会.慢性乙型肝炎诊断标准(2010年版)[J].中西医结合肝病志,2010,21(2)：121-122.
[9]Network NCC.2010NCCN肿瘤学临床实践指南[EB/http://www.nccn-asia.org/cn/default.aspx
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[11]阮秀花,张效本,任丽君等.乙型肝炎病毒感染与原发性肝癌发生的关系[J].中华适宜诊疗技术杂志,2004,22(1)：8-10.
[12]Block TM, Comunale MA, Lowmom M, et al. Use of targeted glycoproteomics to identify serum glycoproteins that correlate with liver cancer in woodchucks and humans [J].PNAS,2005,102(3):779-784.
[13]徐天祥.联合检测血清AFU和AFP对原发性肝癌的诊断价值[J].南方医科大学学报,2008,28(2)：242-243.
[14]林铁军.慢性病毒性肝炎患者血清中甲胎蛋白的检测及临意义[J].中国医药导报,2008,5(16)：97-98.
[15]李利军,李新丰,王高雄.GP73联合AFP^ VEGF检测对原发性肝癌的诊断价值[J].世界华人消化志,2009,17(29)：3056-3060.
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[18]李淑群,陈谦.GP73与肝脏疾病关系的研究进展[J].世界华人消化杂志,2010,18(20)：2117-2120.
[19]朱国民,周晓庆,林长青.新肝癌标志物高尔基体蛋白GP73在肝癌血清学诊断中的应用[J].中华医院感染学杂志,2010,20(15)：2350-2352.
[20]Puri S, Bach ert C, Fimm el CJ, et al. Cycling of early Golgiproteins via the cell surface and endosomes upon lum enal pH disruption [J]. Traffic, 2002,3(9):641-653.
[21]Bachert C, Fimmel C, Linst edt AD. Endosomal trafficking and proprotein convert as ecleavage of cis Golgi protein GP73 produces marker for hepatocellular carcinoma[J]. Traffic,2007,8(10):1415-1423.
[22]Wei S, Dunn TA, Isaacs WB, De Marzo AM, Luo J. GOLPH2 and MYO6:
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[4]Kladney RD, Cui Xiaoyen, Bulla GA, et al. Expression of GP73, a resident golgi membrane protein, in viral and non-viral liver disease[J]. Hepatology, 2002,35(6):1431-1440.
[5]Iftikhar R, Kladney RD, Havlioglu N, et al. Disease-and cell-specific expression of GP73 in human liver disease[J]. Am J Gastroenterol,2004, 99(6):1087-1095.
[6]Block TM, Comunale MA, Lowman M, et al. Use of targeted glycolproteomics to identify serum glycoproteins that correlate with liver cancer in woodchucks and humans[J]. Proc Natl Acad Sci USA,2005, 102(3):779-784.
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[2]Llovet JM, Burroughs A, Bruix J. Hepatocellular carcinoma. Lancet,2003, 362(9399):1907-1917. (PubMed)
[3]王树声,张振权,黄天壬,等.广西90年代初人口死亡原因抽样调查研究[J].广西预防医学,2005,11(3)：40-45.
[4]徐海峰,杨华瑜,张宏冰,等.改变肝癌早期诊断和治疗现状的新肝癌血清标志物.基础医学与临床,2008,28(1)：104-108.
[5]Marrero J, Romano P. GP73, a resident Golgi glyooprotein, is a novel serum marker for hepatocellular carcinoma. J Hepatol,2005,43(6):1007-1012.
[6]毛一雷,杨华瑜,徐海峰等.新的肝癌血清标记物GP73肝癌诊断中的初步研究.中华医学杂志,2008,88(14)：948-951.
[7]原发性肝癌诊疗规范(2011年版)[J].临床肿瘤学杂志,2011,(10)：929-946.
[8]中华医学会肝病学分会,中华医学会感染病学分会.慢性乙型肝炎诊断标准(2010年版)[J].中西医结合肝病志,2010,21(2)：121-122.
[9]Network NCC.2010NCCN肿瘤学临床实践指南[EB/http://www.nccn-asia.org/cn/default.aspx
[10]李谨峰,林川.血清肿瘤标志联合检测对原发性肝癌诊断价值的探讨[J].中华肿瘤防治杂志,2010,17(11)：877-879
[11]阮秀花,张效本,任丽君等.乙型肝炎病毒感染与原发性肝癌发生的关系[J].中华适宜诊疗技术杂志,2004,22(1)：8-10.
[12]Block TM, Comunale MA, Lowmom M, et al. Use of targeted glycoproteomics to identify serum glycoproteins that correlate with liver cancer in woodchucks and humans [J].PNAS,2005,102(3):779-784.
[13]徐天祥.联合检测血清AFU和AFP对原发性肝癌的诊断价值[J].南方医科大学学报,2008,28(2)：242-243.
[14]林铁军.慢性病毒性肝炎患者血清中甲胎蛋白的检测及临意义[J].中国医药导报,2008,5(16)：97-98.
[15]李利军,李新丰,王高雄.GP73联合AFP^ VEGF检测对原发性肝癌的诊断价值[J].世界华人消化志,2009,17(29)：3056-3060.
[16]Kladney RD, Cui X, Bulla GA, Brunt EM, Fimmel CJ. Expression of GP73, a resident golgi membrane protein, in viral and nonviral liver disease. Hepatology 2002;35(6):1431-1440.
[17]Kladney RD, Bulla GA, Guo L, Mason AL, Tollefson AE, Simon DJ, et al.GP73, a novel golgi-localized protein upregulated by viral infection. Gene,2000,249(12):53-65..
[18]李淑群,陈谦.GP73与肝脏疾病关系的研究进展[J].世界华人消化杂志,2010,18(20)：2117-2120.
[19]朱国民,周晓庆,林长青.新肝癌标志物高尔基体蛋白GP73在肝癌血清学诊断中的应用[J].中华医院感染学杂志,2010,20(15)：2350-2352.
[20]Puri S, Bach ert C, Fimm el CJ, et al. Cycling of early Golgiproteins via the cell surface and endosomes upon lum enal pH disruption [J]. Traffic, 2002,3(9):641-653.
[21]Bachert C, Fimmel C, Linst edt AD. Endosomal trafficking and proprotein convert as ecleavage of cis Golgi protein GP73 produces marker for hepatocellular carcinoma[J]. Traffic,2007,8(10):1415-1423.
[22]Wei S, Dunn TA, Isaacs WB, De Marzo AM, Luo J. GOLPH2 and MYO6:
[1]Bruix J, Sherman M. Management of hepatocellular carcinoma[J]. Hepatology,2005,42(5):1208-1236.
[2]Perkins GL, Slater ED, Sanders GK, et al. Serum tumor markers. Am Fam Physician,2003,68(6):1075-1082.
[3]Kladney RD, Bulla GA, Guo Linsheng, et al. GP73, a novel golgi-localized protein upregulated by viral infection[J]. Gene,2000,249(12):53-65.
[4]Kladney RD, Cui Xiaoyen, Bulla GA, et al. Expression of GP73, a resident golgi membrane protein, in viral and non-viral liver disease[J]. Hepatology, 2002,35(6):1431-1440.
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