肝细胞癌Wnt信号通路差异表达基因的筛选及意义  

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

作　　者：叶映泉 朱忠政[1] 王亮亮[1] 鲍玲玲[1] 丛文铭[2] 闻炳基[1] 

机构地区：[1]安徽医科大学宁波学院解放军第一一三医院肿瘤科,浙江宁波315040 [2]第二军医大学东方肝胆外科医院病理科,200438

出　　处：《临床肿瘤学杂志》2016年第11期980-984,共5页Chinese Clinical Oncology

基　　金：南京军区医学科技创新基金(14ZD07;08MA023);宁波自然科学基金(2009A610126)

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。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 relat- ed 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, SFRPS, FZDI 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= 1.07x 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 path- way activation, and its biological and pathological significance in HCC merits further investigations.

关 键 词：肝细胞癌 WNT信号传导通路 差异表达基因 寡核苷酸芯片 

分 类 号：R735.7[医药卫生—肿瘤]