临床肿瘤学杂志

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肠型胃癌中LDH-A与HDAC1表达的相关性研究

张永杰1,秦叔逵2,王杰军3,王喜3,于观贞3,陈颖4   

  1. 1 淮安淮安市第二人民医院肿瘤科 2 解放军八一医院全军肿瘤中心肿瘤内科 3 上海长征医院肿瘤科 4 上海长海医院病理科
  • 收稿日期:2013-10-08 修回日期:2013-10-28 出版日期:2013-12-31 发布日期:2013-12-31
  • 通讯作者: 秦叔逵,王杰军

The relationship between the expression of LDH-A and HDAC1 in intestinaltype gastric cancer

ZHANG Yongjie, QIN Shukui, WANG Jiejun, WANG Xi, YU Guanzhen, Chen Ying.   

  1. Department of Oncology,Huai'an Second People's Hospital
  • Received:2013-10-08 Revised:2013-10-28 Online:2013-12-31 Published:2013-12-31
  • Contact: QIN Shukui, WANG Jiejun

摘要: 目的 探讨乳酸脱氢酶A(LDH-A)与组蛋白去乙酰化酶1(HDAC1)在肠型胃癌中表达的相关性及其与预后的关系。方法 应用Western blotting法检测HDAC1蛋白在慢病毒介导的LDHA siRNA转染肠型胃癌细胞株SGC7901中表达的变化;应用免疫组织化学方法检测661例肠型胃癌组织及癌旁正常组织中LDH-A与HDAC1蛋白的表达情况并分析其表达与预后的关系。结果 Western blotting检测结果显示,LDH-A蛋白在SGC7901细胞株中的表达明显上调,且LDH-A的沉默可显著下调HDAC1的表达。肠型胃癌组织中LDH-A蛋白的高表达率为54.8%(362/661),明显高于癌旁正常组织的12.9%(85/661),两者差异有统计学意义(P<0.01);肠型胃癌组织中HDAC1的高表达率为51.3%(339/661),明显高于癌旁正常组织的15.4%(102/661),两者差异有统计学意义(P<0.01)。LDH-A与HDAC1蛋白在肠型胃癌组织中的表达呈正相关(r=0.324, P<0.001)。单因素生存分析结果显示,LDH-A与HDAC1均低表达患者的生存曲线明显优于其他组合(P<0.001);多因素生存分析结果显示LDH-A与HDAC1表达均为肠型胃癌独立的预后因素。
结论在肠型胃癌中, LDH-A与HDAC1的表达呈正相关,采用LDH-A和HDAC1双靶点抑制治疗可能具有潜在的生存获益。

Abstract: Objective To investigate the correlation between the expression of lactate dehydrogenase A(LDH-A) and histone deacetylase 1(HDAC1) in intestinaltype gastric cancer(ITGC) and analyze the relationship between their expressions and prognosis. Methods The LDH-A siRNAexpressing lentiviral vector was constructed and used to transfect into ITGC cell line SGC7901. Western blotting was applied to detect the expression of HDAC1 protein. The expressions of LDH-A and HDAC1 in 661 ITGC specimens and the corresponding noncancerous tissues were performed by immunohistochemistry technique. Results According to Western blotting results, LDH-A expression was significantly upregulated in SGC7901 cells and the knockdown of LDH-A in SGC7901 cells significantly downregulated the expression of HDAC1. Based on the analysis of immunohistochemistry results, the high expression rate of LDH-A protein in ITGC was 54.8%(362/661),significantly higher than 12.9%(85/661)in paired adjacent noncancerous tissues(P<0.01); the high expression rate of HDAC1 protein in ITGC was 51.3%(339/661), significantly higher than 15.4%(102/661) in paired adjacent noncancerous tissues(P<0.01); LDHA expression was positively related to HDAC1 expression(r=0.324, P<0.001). Univariate analysis showed that the survival curve of patients with low LDH-A/low HDAC1 expression was significantly better than that of other combinations in ITGC(P<0.001). Multivariate survival analysis showed that LDHA and HDAC1expression were independent prognostic factors.
ConclusionThe expressions of LDH-A and HDAC1 have positive correlation in ITGC. Targeted inhibition of both LDH-A and HDAC1 is promising to bring longer overall survival.

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