王宁, 杨斌, 骆莹, 王涛, 王凤梅, 高英堂, 杜智. Wnt途径拮抗剂Dickkopf-3蛋白在肝细胞癌中表达亚细胞定位及临床意义[J]. 中国肿瘤临床, 2012, 39(2): 93-96, 104. DOI: 10.3969/j.issn.1000-8179.2012.02.009
引用本文: 王宁, 杨斌, 骆莹, 王涛, 王凤梅, 高英堂, 杜智. Wnt途径拮抗剂Dickkopf-3蛋白在肝细胞癌中表达亚细胞定位及临床意义[J]. 中国肿瘤临床, 2012, 39(2): 93-96, 104. DOI: 10.3969/j.issn.1000-8179.2012.02.009
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Ning WANG, Bin YANG, Ying LUO, Tao WANG, Fengmei WANG, Yingtang GAO, Zhi DU. Expression, Subcellular Localization, and Clinical Implication of Wnt Antagonist Dickkopf-3 in Hepatocellular Carcinoma[J]. CHINESE JOURNAL OF CLINICAL ONCOLOGY, 2012, 39(2): 93-96, 104. DOI: 10.3969/j.issn.1000-8179.2012.02.009
Citation: Ning WANG, Bin YANG, Ying LUO, Tao WANG, Fengmei WANG, Yingtang GAO, Zhi DU. Expression, Subcellular Localization, and Clinical Implication of Wnt Antagonist Dickkopf-3 in Hepatocellular Carcinoma[J]. CHINESE JOURNAL OF CLINICAL ONCOLOGY, 2012, 39(2): 93-96, 104. DOI: 10.3969/j.issn.1000-8179.2012.02.009
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Wnt途径拮抗剂Dickkopf-3蛋白在肝细胞癌中表达亚细胞定位及临床意义

Expression, Subcellular Localization, and Clinical Implication of Wnt Antagonist Dickkopf-3 in Hepatocellular Carcinoma

    摘要
  • 摘要:
      目的  分析Wnt途径拮抗剂Dickkopf-3(DKK3)蛋白在肝细胞癌中表达和亚细胞定位, 探讨其在肝细胞癌中的临床意义。
      方法  采用细胞免疫荧光和免疫组织化学方法, 分析肝癌细胞系及43例肝细胞癌与相应癌旁组织中DKK3的蛋白表达, 并对其中31例中DKK3基因的甲基化状态进行检测。
      结果  DKK3蛋白在肝细胞癌组织中的高表达率为67.4%(29/43), 显著高于相应癌旁组织中的41.8%(18/43)(P=0.017), 且细胞核内呈明显高表达; 肝细胞癌组织中DKK3基因甲基化发生率为90.3%(28/31), 显著高于相应的癌旁组织中的64.5%(20/31)(P=0.015), DKK3基因的甲基化状态与蛋白表达无明显相关性(P=0.844);DKK3低表达的肝细胞癌患者5年总生存率和无瘤生存率明显高于高表达者(P=0.049, P=0.001)。
      结论  肝细胞癌中DKK3基因的甲基化状态可能与肝细胞癌中DKK3蛋白表达呈负相关; DKK3在癌组织中的高表达可能对肝细胞癌具有促进而非抑制性作用, 可以作为判断肝细胞癌预后的指标。

     

    Abstract:
      Objective  To analyze the expression and subcellular localization of Wnt antagonist Dickkopf-3 (DKK3) in hepatocellular carcinoma (HCC) and to investigate the clinical implication of DKK3 expression in HCC.
      Methods  DKK3 protein expression in the liver cancer cell line, 43 tissue samples of HCC and corresponding adjacent tissue, was examined with immunofluorescence or immunohistochemistry. The DKK3 methylation status was then assayed by methylation-specific PCR in 31 cases of HCC and paired adjacent tissue.
      Results  High DKK3 protein expression level was observed in 67.4% (29 / 43) of HCC tissue, significantly higher than that in the paired adjacent tissue 41.8 % (18 / 43), P= 0.017, and DKK3 protein was mainly expressed in the cell nucleus. DKK3 gene methylation was detected in 90.3% (28/31) of HCC tissue samples, significantly higher than that in the corresponding adjacent tissue samples 64.5 % (20 / 31), P= 0.015. No correlation was found between DKK3 methylation status and its protein expression (P= 0.844). Patients with low DKK3 expression had higher overall or disease-free survival than those with high expression of this protein (P= 0.049, 0.001).
      Conclusion  No correlation exists between the DKK3 methylation status and its protein expression. High DKK3 expression may promote HCC, and DKK3 protein expression in HCC tissue may be used as a prognostic marker for hepatocellular carcinoma.

     

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