Clinical value of circulating peripheral blood mononuclear cell glypican-3 mRNA and alpha fetoprotein for diagnosing and monitoring metastasis of hepatocellular carcinoma
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摘要:
目的分析肝癌患者外周血单核细胞中磷脂酰肌醇蛋白多糖(GPC)-3 mRNA表达及甲胎蛋白(AFP)对肝癌诊断与转移监测的价值。方法收集住院肝病患者外周血,分离单核细胞,制备总RNA,经逆转录合成GPC-3cDNA,以荧光定量PCR扩增并分析其对肝癌诊断与转移监测的价值。结果外周血单核细胞中GPC-3 mRNA阳性仅见肝癌患者,55例肝癌患者中39例阳性(70.9%);肝硬化、肝炎、转移性肝癌、非肝肿瘤患者及正常对照组中未检出阳性(χ2=26.773,P<0.001)。外周血单核细胞GPC-3 mRNA阳性表达与HBsAg阳性(χ2=14.601,P<0.001)、肝癌的TNM分期(χ2=15.252,P<0.001)、门静脉癌栓(χ2=45.658,P<0.001)及伴肝外转移显著相关(χ2=22.273,P<0.001),与瘤体直径、数目、AFP浓度及分化程度间无明显相关;与血AFP可互补诊断,提高肝癌诊断阳性率(90.9%)。结论循环血单核细胞GPC-3 mRNA分析,有助于肝癌诊断和肝外转移监测,对AFP阴性肝癌具互补诊断价值。
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关键词:
- 肝肿瘤 /
- 磷脂酰肌醇蛋白聚糖类 /
- 甲胎蛋白类
Abstract:Objective To measure the circulating peripheral blood mononuclear cell (PBMC) expression of glypican-3 (GPC-3) and levels of alpha fetoprotein (AFP) and assess their values for diagnosing and monitoring metastasis of hepatocellular carcinoma (HCC) .Methods Total RNA was extracted from PBMCs of patients with HCC (n=55) , liver cirrhosis (n=20) , chronic hepatitis (n=20) , metastatic HCC (n=20) , non-liver tumors (n=20) , and normal controls (n=20) .GPC-3 gene expression was measured by fluorescence reverse transcription quantitative PCR.Intergroup differences were assessed by the Chi-squared test or Fisher's exact test.Results Positive expression of GPC-3 mRNA in PBMCs was only detected in HCC patients (70.9% vs.0 in all other groups;χ2=26.773, P<0.001) .Furthermore, the expression of GPC-3 mRNA in PBMCs was associated with HBV infection (χ2=14.601, P<0.001) , TNM stage (χ2=15.252, P<0.001) , periportal cancerous embolus (χ2=45.658, P<0.001) , and extrahepatic metastasis (χ2=22.273, P<0.001) .No relation was found between GPC-3 mRNA in PBMCs and size of tumors, number of tumors, AFP level, or tumor differentiation degree.The AFP-positive rate for HCC patients was 63.6%.The combination of GPC-3 up-regulated expression in PBMCs and enhanced serum AFP was found in 90.9% of HCC patients.Conclusion The GPC-3 mRNA level in circulating PBMCs and serum AFP level may be useful biomarkers for diagnosing HCC and its metastasis.
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Key words:
- liver neoplasms /
- glypicans /
- alpha-fetoproteins
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[1]Aravalli RN, Steer CJ, Cressman EN.Molecular mechanismsof hepatocellular carcinoma[J].Hepatology, 2008, 48 (6) :2047-2063. [2]Qian J, Yao D, Dong Z, et al.Characteristics of hepatic igf-ii expression and monitored levels of circulating igf-ii mRNAin metastasis of hepatocellular carcinoma[J].Am J ClinPathol, 2010, 134 (5) :799-806. [3]Yao M, Yao DF, Bian YZ, et al.Oncofetal antigen glypican-3 as a promising early diagnostic marker for hepatocellularcarcinoma[J].Hepatobiliary Pancreat Dis Int, 2011, 10 (3) :289-294. [4]中国抗癌协会肝癌专业委员会.原发性肝癌的临床诊断与分期标准[J].中华肝脏病杂志, 2001, 9 (6) :324-325. [5]张崇国, 姚登福, 吴玮, 等.肝细胞癌变过程中磷脂酰肌醇蛋白多糖-3mRNA扩增及临床值[J].江苏医药, 2009, 34 (3) :308-310. [6]O'Beirne J, Farzaneh F, Harrison PM.Generation of functionalCD8+T cells by human dendritic cells expressing glypican-3epitopes[J].J Exp Clin Cancer Res, 2010, 29 (1) :48-58. [7]Kandil D, Leiman G, Allegretta M, et al.Glypican-3 immu-nocytochemistry in liver fine-needle aspirates:a novel stainto assist in the differentiation of benign and malignant liver le-sions[J].Cancer, 2007, 111 (5) :316-322. [8]Yang D, Yang J, Lu F, et al.A new membrane re-an-chored protein originating from GPC3 against hepatoma cellsHepG2[J].Mol Med Report, 2011, 4 (6) :1067-1073. [9]El Tayebi HM, Salah W, El Sayed IH, et al.Expression of insulin-like growth factor-II, matrix metalloproteinases, and theirtissue inhibitors as predictive markers in the peripheral blood ofHCC patients[J].Biomarkers, 2011, 16 (4) :346-354. [10]Yan D, He Q, Chen Y, et al.Detection ofα-fetoproteinand glypican-3 mRNAs in the peripheral blood of hepatocel-lular carcinoma patients by using multiple FQ-RT-PCR[J].J Clin Lab Anal, 2011, 25 (2) :113-117. [11]Wang YX, Meng XW, Wang YD, et al.mRNA levels of twodifferent enzymes in hepatocellular carcinoma[J].Hepato-gastroenterology, 2010, 57 (102-103) :1187-1190. [12]Suzuki M, Sugimoto K, Tanaka J, et al.Up-regulation ofglypican-3 in human hepatocellular carcinoma[J].Antican-cer Res, 2010, 30 (12) :5055-5061. [13]Shirakawa H, Suzuki H, Shimomura M, et al.Glypican-3expression is correlated with poor prognosis in hepatocellularcarcinoma[J].Cancer Sci, 2009, 100 (8) :1403-1407.
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