Li Wenfeng, Liu Jia, Zou Di, Cai Xiaye, Wang Jingying, Wang Jinmeng, Zhu Li, Zhao Liang, Ou Rongying, Xu Yunsheng
Laboratory for Advanced Interdisciplinary Research, Center for Personalized Medicine/Institutes of Translational Medicine, The First Affiliated Hospital of Wenzhou Medical University, Ouhai, Wenzhou, Zhejiang 325000, P.R. China.
Oncol Rep. 2017 Mar;37(3):1461-1468. doi: 10.3892/or.2017.5433. Epub 2017 Feb 7.
To explore the complex molecular mechanisms of bladder cancer, mRNA and miRNA expression profiles were combined for systematic analyses. A total of 18 common differentially expressed genes (DEGs) were identified from two mRNA expression datasets which consisted of 206 tumor and 74 normal tissues. Then, survival analysis based on the SurvExpress database showed that the common DEGs were able to significantly differentiate low- and high-risk groups in 4 public bladder cancer datasets (p<0.01). Notably, the tumor and normal samples were able to be almost clearly classified into 4 groups based on these identified common DEGs. In addition, 6 out of the 18 common DEGs, including ALDH1A1 and SRPX, are regulated by 6 reported miRNAs based on regulatory network analyses. Expression levels of the 6 DEGs were validated in 10 bladder cancer samples using RT-PCR, and the expression values were concordant with the microarray results. Collectively, our analyses indicated that various biological processes are involved in the development and progression of bladder cancer. Firstly, cell cycle checkpoints and DNA repair networks of cancer stem-like cells were regulated by high expression of ALDH1A1, and hence promoted tumor self-renewal or metastasis. Then, activation of HspB6 induced the angiogenesis process which provides necessary nutrition and oxygen for tumor cells. Moreover, downregulation of the expression of tumor-suppressor genes SRPX and FLNC further promoted apoptosis and metastasis. The identification of potential biological processes and genes can be helpful for the understanding of bladder cancer molecular mechanisms.
为了探究膀胱癌复杂的分子机制，我们对mRNA和miRNA表达谱进行了综合系统分析。从两个包含206个肿瘤组织和74个正常组织的mRNA表达数据集中，共鉴定出18个常见的差异表达基因（DEGs）。随后，基于SurvExpress数据库的生存分析表明，这些常见的DEGs能够在4个公开的膀胱癌数据集中显著区分低风险和高风险组（p<0.01）。值得注意的是，基于这些鉴定出的常见DEGs，肿瘤样本和正常样本几乎能够被清晰地分为4组。此外，根据调控网络分析，18个常见DEGs中的6个，包括ALDH1A1和SRPX，受6个已报道的miRNAs调控。使用RT-PCR在10个膀胱癌样本中验证了这6个DEGs的表达水平，其表达值与微阵列结果一致。总体而言，我们的分析表明，多种生物学过程参与了膀胱癌的发生和发展。首先，癌症干细胞样细胞的细胞周期检查点和DNA修复网络受ALDH1A1高表达调控，从而促进肿瘤自我更新或转移。其次，HspB6的激活诱导了血管生成过程，为肿瘤细胞提供了必要的营养和氧气。此外，抑癌基因SRPX和FLNC表达的下调进一步促进了细胞凋亡和转移。潜在生物学过程和基因的鉴定有助于理解膀胱癌的分子机制。
