Fang Z-Q, Zang W-D, Chen R, Ye B-W, Wang X-W, Yi S-H, Chen W, He F, Ye G
Department of Urology, Center of Nephrology, The Second Affiliated Hospital, The Third Military Medical University, Chongqing, China.
Genet Mol Res. 2013 May 6;12(2):1479-89. doi: 10.4238/2013.May.6.1.
Bladder cancer is a highly heterogeneous neoplasm. We examined the gene expression profile in 3 bladder cancer stages (Ta, T1, T2) using expression microarray analysis of 40 bladder tumors. Differentially expressed genes were found by the t-test, with <0.005 as the significance threshold. KEGG pathway-enrichment analysis was used to study the signaling pathways of the genes. We found 36 genes that could be used as molecular markers for predicting the transition from Ta-T1 to T1-T2. Among these, 11 overlapped between Ta-T1 and T1-T2 stages. Six genes were down-regulated at the Ta-T1 stage, but were up-regulated at the T1-T2 stage (ANXA5, ATP6V1B2, CTGF, GEM, IL13RA1, and LCP1); 5 genes were up-regulated at the Ta-T1 stage, but down-regulated at the T1-T2 stage (ACPP, GNL1, RIPK1, RAPGEF3, and ZER1). Another 25 genes changed relative expression levels at the T1-T2 stage. These genes (including COL1A1, COL1A2, FN1, ITGA5, LGALS1, SPP1, VIM, POSTN, and COL18A1) may be involved in bladder cancer progression by affecting extracellular matrix-receptor interaction and focal adhesion. The cytokine-cytokine receptor interaction, neuroactive ligand-receptor interaction, and calcium-signaling pathway were associated with bladder cancer progression at both the Ta-T1 and T1-T2 stages.
膀胱癌是一种高度异质性肿瘤。我们使用40例膀胱肿瘤的表达微阵列分析，检测了3个膀胱癌阶段（Ta、T1、T2）的基因表达谱。通过t检验发现差异表达基因，显著性阈值为<0.005。使用KEGG通路富集分析来研究这些基因的信号通路。我们发现36个基因可作为预测从Ta-T1期向T1-T2期转变的分子标志物。其中，11个基因在Ta-T1期和T1-T2期重叠。6个基因在Ta-T1期下调，但在T1-T2期上调（ANXA5、ATP6V1B2、CTGF、GEM、IL13RA1和LCP1）；5个基因在Ta-T1期上调，但在T1-T2期下调（ACPP、GNL1、RIPK1、RAPGEF3和ZER1）。另外25个基因在T1-T2期改变了相对表达水平。这些基因（包括COL1A1、COL1A2、FN1、ITGA5、LGALS1、SPP1、VIM、POSTN和COL18A1）可能通过影响细胞外基质-受体相互作用和粘着斑参与膀胱癌进展。细胞因子-细胞因子受体相互作用、神经活性配体-受体相互作用和钙信号通路在Ta-T1期和T1-T2期均与膀胱癌进展相关。
