Zeng Bin, Zhao Qiting, Sun Zhiwei, Liu Doudou, Chen Hao, Li Xiaoshuang, Wang Jianyu, Xing H Rosie
Institute of Life Sciences, Chongqing Medical University, Chongqing, China.
State Key Laboratory of Ultrasound Engineering in Medicine Co-Founded By Chongqing and the Ministry of Science and Technology, School of Biomedical Engineering, Chongqing Medical University, Chongqing, China.
Front Genet. 2021 Aug 11;12:672832. doi: 10.3389/fgene.2021.672832. eCollection 2021.
Clinical data mining and bioinformatics analysis can be employed effectively to elucidate the function and underlying mechanisms of the gene of interest. Here, we have proposed a framework for the identification and validation of independent biomarkers in human cancer and for mechanistic profiling using gene sets enrichment analysis and pathway analysis. This is followed by validation with experiments. Using this framework to analyze the clinical relevance of SEC23A, we have discovered the prognostic potential of SEC23A in different cancers and identified SEC23A as an independent prognostic factor for poor prognosis in bladder cancer, which implicates SEC23A, for the first time, as an oncogene. Bioinformatic analyses have elucidated an association between SEC23A expression and the upregulation of the MAPK signaling pathway. Using the T24 human bladder cell line, we confirmed that knockdown of SEC23A expression could effectively impact the MAPK signaling pathway. Further, through PCR verification, we showed that MEF2A, one of the key genes of the MAPK signaling pathway, might be a downstream factor of the SEC23A gene.
临床数据挖掘和生物信息学分析可有效地用于阐明感兴趣基因的功能和潜在机制。在此,我们提出了一个框架,用于识别和验证人类癌症中的独立生物标志物,并使用基因集富集分析和通路分析进行机制剖析。随后通过实验进行验证。利用该框架分析SEC23A的临床相关性,我们发现了SEC23A在不同癌症中的预后潜力,并确定SEC23A是膀胱癌预后不良的独立预后因素,这首次将SEC23A牵连为一种癌基因。生物信息学分析阐明了SEC23A表达与MAPK信号通路上调之间的关联。使用T24人膀胱癌细胞系,我们证实敲低SEC23A表达可有效影响MAPK信号通路。此外,通过PCR验证,我们表明MAPK信号通路的关键基因之一MEF2A可能是SEC23A基因的下游因子。