Xiong Yaoyi, Yuan Lushun, Chen Liang, Zhu Yuan, Zhang Shanshan, Liu Xuefeng, Xiao Yu, Wang Xinghuan
Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China.
Department of Biological Repositories, Zhongnan Hospital of Wuhan University, Wuhan, China.
J Cancer. 2018 Oct 10;9(21):3912-3922. doi: 10.7150/jca.25900. eCollection 2018.
Although it is well known that smoking is one of pathogenesis of clear cell renal cell carcinoma (ccRCC), the underlying molecular mechanism is still unclear. In our study, the microarray dataset GSE46699 is analyzed by weighted gene co-expression network analysis (WGCNA). Then we identify 15 co-expressed gene modules in which the lightcyan module (R = 0.30) is the most significant. Combined with the protein-protein interaction (PPI) network and WGCNA, two hub genes are identified. Meanwhile, linear regression analyses indicate that has a higher connection with smoking in ccRCC, survival analysis proved that overexpression of in ccRCC could lead to shorter survival time. Furthermore, bioinformatical analyses based on GSE46699 and GSE2109 as well as qRT-PCR experiment show similar results that is significantly up-regulated in smoking ccRCC compared to non-smoking ccRCC samples. In addition, Functional analysis, pathway enrichment analysis and gene set enrichment analysis (GSEA) indicate that high expression of is related to cell cycle and p53 signaling pathway in ccRCC samples. Moreover, experiments revealed that induced cell cycle arrest at G2 phase and proliferation inhibition via p53 phosphorylation. Taken together, by using WGCNA, we have identified a novel biomarker named , which could affect the development of smoking-related ccRCC by regulating cell cycle and p53 signaling pathway.
尽管众所周知吸烟是透明细胞肾细胞癌（ccRCC）的发病机制之一，但其潜在的分子机制仍不清楚。在我们的研究中，通过加权基因共表达网络分析（WGCNA）对微阵列数据集GSE46699进行了分析。然后我们识别出15个共表达基因模块，其中浅青色模块（R = 0.30）最为显著。结合蛋白质-蛋白质相互作用（PPI）网络和WGCNA，确定了两个枢纽基因。同时，线性回归分析表明，在ccRCC中与吸烟有更高的关联性，生存分析证明ccRCC中该基因的过表达会导致较短的生存时间。此外，基于GSE46699和GSE2109的生物信息学分析以及qRT-PCR实验显示了相似的结果，即与非吸烟ccRCC样本相比，吸烟ccRCC中该基因显著上调。另外，功能分析、通路富集分析和基因集富集分析（GSEA）表明，该基因的高表达与ccRCC样本中的细胞周期和p53信号通路相关。此外，实验表明该基因通过p53磷酸化诱导细胞周期停滞在G2期并抑制增殖。综上所述，通过使用WGCNA，我们确定了一个名为的新型生物标志物，它可以通过调节细胞周期和p53信号通路影响吸烟相关ccRCC的发展。
