临床肿瘤学杂志

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肝细胞癌Wnt信号通路差异表达基因的筛选及意义

叶映泉1,朱忠政1,王亮亮1,鲍玲玲1,丛文铭2,闻炳基1   

  1. 1 安徽医科大学宁波学院解放军第一一三医院肿瘤科 2 第二军医大学东方肝胆外科医院病理科
  • 收稿日期:2016-07-11 修回日期:2016-09-12 出版日期:2016-11-30 发布日期:2016-11-30
  • 通讯作者: 闻炳基

Screening of differentially expressed Wnt signaling pathway genes in hepatocellular carcinoma and its significance

YE Yingquan, ZHU Zhongzheng,WANG Liangliang, BAO Lingling, CONG Wenming, WEN Bingji.   

  1. Department of Oncology, No.113 Hospital of Peoples Liberation Army
  • Received:2016-07-11 Revised:2016-09-12 Online:2016-11-30 Published:2016-11-30
  • Contact: WEN Bingji

摘要: 目的 检测肝细胞癌(HCC)中Wnt信号传导通路相关基因的差异表达情况,探讨HCC与该信号通路的关系。方法 采用Affymetrix U133 Plus2.0基因芯片检测93例HCC及其配对癌旁组织中78个Wnt信号通路相关基因的mRNA表达差异。结果 与癌旁肝组织相比,HCC组织中TCF19、MMP-12、DKK1、Bcl-9、SFRP4、MMP-1、PYGO2、FZD6、MMP-9、Wnt6共10个基因表达上调,而SFRP1、TCF21、SFRP5、FZD1、Wnt2共5个基因表达下调。其中,TCF19表达上调倍数最多,达9.61倍(P=1.07×10-26)。TCF19表达与FZD1、FZD6、Bcl9、Wnt6、MMP1和MMP12表达呈正相关(均P<0.05)。TCF19表达与肿瘤数目(P=0.017)和分化程度(P=0.046)有关。结论 HCC中存在Wnt信号通路多基因异常表达。下游转录因子TCF19高表达可能是Wnt信号通路激活的关键终末效应,其在HCC中的生物学和病理学意义有待进一步研究。

Abstract: Objective To detect the differentially expressed Wnt signaling pathway genes in hepatocellular carcinoma (HCC), and investigate the relationship between HCC and Wnt signaling pathway. Methods The expression levels of 78 genes related Wnt signaling pathway were measured using Affymetrix GeneChip Human Genome U133 Plus 20 array in 93 cases of HCC tissues and paired nontumor liver tissues.
Results A total of 10 up-regulated genes (TCF19, MMP-12, DKK1, Bcl-9, SFRP4, MMP-1, PYGO2, FZD6, MMP-9 and Wnt6), and 5 down-regulated genes (SFRP1, TCF21, SFRP5, FZD1 and Wnt2) were identified to be significantly differentially expressed in HCC tissues, compared with paired non-tumor liver tissues. The expression level of TCF19, the most overexpressed gene in this series (fold change=9.61, P=1.07×10-26), was significantly correlated with FZD1, FZD6, Bcl-9, Wnt6, MMP-1 and MMP-12 (P<0.05). The expression of TCF19 was significantly associated with the number of tumor (P=0.017) and Edmondson-Steiner grade (P=0.046). Conclusion Multiple differentially expressed genes in Wnt signaling pathway in HCC are screened. Increased expression of TCF19, a downstream transcription factor, may be the key terminal effect of the Wnt signaling pathway activation, and its biological and pathological significance in HCC merits further investigations.

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