肝细胞癌患者肿瘤坏死因子相关凋亡诱导配体的基因多态性与血清水平的临床意义
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山东省医药卫生科技发展计划(2013WS0185);山东省高等学校科技计划项目(J10LC24)。


Genetic polymorphism of tumor necrosis factor related apoptosis-inducing ligand(TRAIL) and TRAIL protein in serum: clinical significance in hepatocellular carcinoma patients
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    摘要:

    摘要:目的:探讨肝细胞癌(HCC)患者肿瘤坏死因子相关凋亡诱导配体(TRAIL)基因多态性及血清可溶性TRAIL(sTRAIL)水平及临床意义。 方法:收集HCC患者173例和健康人对照170例,提取全血基因组DNA,用测序法和PCR-限制性片段长度多态性(PCR-RFLP)法分析TRAIL基因第5外显子3′端非编码区(UTR)1289C/T、1525G/A、1588G/A、1595C/T基因多态性;用ELISA法检测血清sTRAIL浓度;用电化学发光法和生化定量分析法分别检测血清甲胎蛋白(AFP)和α-L岩藻糖苷酶(AFU)浓度。 结果:HCC组与对照组比较,1289C/T、1588G/A、1595C/T基因型分布差异均有统计学意义(P<0.05);HCC组1289C、1525G、1588G、1595C等位基因频率明显高于对照组(P<0.05)。HCC组血清sTRAIL水平(78.8±49.2) pg/mL明显低于对照组(106.2±64.4) pg/mL(P<0.05);根据TNM分期,Ⅰ、Ⅱ期HCC患者sTRAIL浓度明显高于Ⅲ、Ⅳ期(P均<0.05)。HCC组根据TNM分期和肿瘤大小分组,TRAIL基因1289C/T、1525G/A、1588G/A、1595C/T位点基因型分布差异无统计学意义(P均>0.05);根据TRAIL基因各位点基因型分组,组间血清sTRAIL水平差异均无统计学意义(P均>0.05);HCC患者sTRAIL浓度与血清AFP、AFU浓度无相关性(P>0.05)。 结论:TRAIL基因(1289C/T、1525G/A、1588G/A、1595C/T)多态性及血清sTRAIL水平与HCC发生、发展可能相关,此结论还需继续研究。

    Abstract:

    Abstract:Objective:To explore the clinical significance of genetic polymorphisms of tumor necrosis factor related apoptosis inducing ligand(TRAIL) and the solute TRAIL(sTRAIL) in serum of hepatocellular carcinoma patients. 〖WTHZ〗Methods〖WTBZ〗〓In total, 173 cases with hepatocellular cancer and 170 healthy controls were selected and the genomic DNAs were extracted from peripheral blood. The polymorphisms of TRAIL gene in the 3′-UTR of exon 5 at the positions of 1289C/T, 1525G/A, 1588G/A and 1595C/T were detected by sequencing analysis and polymerase chain reaction restriction fragment length polymorphism(PCR-RFLP) method. The serum levels of sTRAIL were determined by ELISA. The levels of serum alpha fetoprotein(AFP) in serum were measured by electrochemical luminescence and alpha L-fucosidase(AFU) were determined by biochemical quantitative method. Results:Significant differences were found in the distribution of 1289C/T, 1588G/A, 1595C/T genotype between hepatocellular carcinoma group and control group. The frequencies of 1289C, 1525G, 1588G, 1595C alleles in hepatocellular carcinoma group were significantly higher than those in controls(P<0.05). The levels of serum sTRAIL in hepatocellular carcinoma group(78.8±49.2) pg/mL were significantly lower than those in controls(106.2±64.4)pg/mL(P<0.05). According to TNM staging of hepatocellular carcinoma group, the levels of serum sTRAIL in phase Ⅰ and Ⅱ were significantly higher than those in phase Ⅲ and Ⅳ(P<0.05). In hepatocellular carcinoma group, no statistical differences of 1289C/T, 1525G/A, 1588G/A, 1595C/T genotype distributions were found in the different subgroup of either TNM staging or tumor size(P>0.05). No significant differences of the levels of serum sTRAIL among all the TRAIL genotype groups(P>0.05) were found. There was no correlation between the levels of sTRAIL and AFP, AFU in the serum of patients(P>0.05). Conclusion:The genetic polymorphisms of TRAIL(1289C/T, 1525G/A, 1588G/A, 1595C/T) and the levels of serum sTRAIL may correlated with the pathogenensis of hepatocellular carcinoma, which should be further studied.

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闫晓华,刘瑞磊,张纪云,吴佳学,董立.肝细胞癌患者肿瘤坏死因子相关凋亡诱导配体的基因多态性与血清水平的临床意义[J].临床检验杂志,2014,(6):418-425

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  • 收稿日期:2014-01-07
  • 最后修改日期:2014-04-19
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  • 在线发布日期: 2014-07-16
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