Screening Of Differentially Expressed Wnt Signaling Pathway Genes In Hepatocellular Carcinoma And Its Significance

Objective: Hepatocellular carcinoma(HCC)is the fifth most common malignancy and the second leading cause of cancer-related in China.Wnt signaling pathway is a very conserved signal transduction pathways that play a key role in biological processes and functions such as embryonic development,tissue regeneration,hematopoiesis,cell proliferation,differentiation and migration.The abnormal activation of the Wnt signaling pathway has been shown to be closely related to the development of multiple tumors,including HCC.HCC is a characteristic tumor in China,but we are still unknown to the expression of Wnt signaling pathway in Chinese HCC.The aim of this study was to screen the differentially expressed genes of Wnt signaling pathway in human HCC,and to investigate the differentially expressed Wnt signaling pathway genes in hepatocellular carcinoma(HCC).Methods: The expression levels of 78 genes were measured using Affymetrix Gene Chip Human Genome U133 Plus 2.0 array in 93 HCCs and paired non-tumor liver tissues.Paired t-test was used to compare the gene expression levels between HCCs and paired non-tumor tissues.Spearman correlation test was used to find the correlation between the differential gene expression levels in the cancer tissue.The correlation analysis between the expression levels of differentially expressed genes and some clinicopathological parameters was analyzed by ?2 test.All data were processed by SPSS 13.0.Results: A total of 10 upregulated genes,TCF19,MMP12,DKK1,BCL9,SFRP4,MMP1,PYGO2,FZD6,MMP9 and WNT6,and 5 downregulated genes,SFRP1,TCF21,SFRP5,FZD1 and WNT2,were identified to be significantly differentially expressed in HCCs,compared to paired non-tumor liver tissues.There was a wide correlation between the expression levels of 15 HCC differentially expressed genes.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 that of FZD1,FZD6,BCL9,WNT6,MMP1 and MMP12(all P < 0.05).Higher TCF19 expression(> median)was significantly associated with multiple tumor(P = 0.017)and higher 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.