NCAPG Is a Promising Therapeutic Target Across Different Tumor Types
NCAPG Is a Promising Therapeutic Target Across Different Tumor Types
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NCAPG 是针对不同肿瘤类型的有前景的治疗靶点。
DOI：
10.3389/fphar.2020.00387
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发表时间：
2020-04-02
影响因子：
5.6
通讯作者：
Zhang, Qi
中科院分区：
文献类型：
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作者：
Xiao, Cuicui;Gong, Jiao;Zhang, Qi
背景随着CRISPR-Cas9基因组编辑工具在基因治疗中的出现，识别异常表达的基因在各种癌症类型中具有重要的价值。因为大量患者可能从分子靶向基因治疗中受益。这项研究的目的是识别不同癌症类型中异常表达的基因，分析预期的机制及其与生存结果的相关性。结果NCAPG在肿瘤基因组图谱数据库(TCGA)中高表达，该数据库包括6,647例癌组织和16种癌类型的647例正常组织的转录本。此外，在16种肿瘤的蛋白质水平上也观察到了预测的NCAPG过表达率。重要的是，高水平的NCAPG与各种癌症类型，如肝细胞癌、乳腺癌、肺癌或卵巢癌的不良生存密切相关。多因素分析表明，NCAPG、TNM和巴塞罗那临床肝癌(BCLC)分期是影响肝癌患者死亡率的独立危险因素。此外，功能和途径丰富分析表明，NCAPG与细胞周期、细胞衰老和错配修复等途径密切相关。通过加权基因共表达网络分析(WGCNA)，我们确定NCAPG是绿松石模块中的一个中枢基因，与肝癌样本的生存时间密切相关。结论据我们所知，这项研究对几种肿瘤类型进行了全面的RNA-SEQ分析，揭示了NCAPG是一个有希望的分子靶点。NCAPG的过表达可能通过调节肿瘤相关途径在肿瘤的发生发展中发挥重要作用，从而拓宽对发病机制的理解，突出开发新的靶向治疗的可能性。
Background With the advent of CRISPR-Cas9 genome editing tool in gene therapy, identification of aberrantly expressed genes is of great value across various cancer types. Since a large number of patients may benefit from molecular targeted gene therapy. The purpose of this study was to identify aberrantly expressed genes across various cancer types, analyze prospective mechanisms and their correlation with survival outcomes. Results NCAPG was highly expressed in The Cancer Genome Atlas (TCGA) database, which includes the transcriptomes of 6,647 cancer and 647 normal tissue samples from 16 cancer types. Furthermore, a predicted NCAPG overexpression rate was also observed at the protein level in 16 tumor types. Importantly, high NCAPG level was significantly associated with unfavorable survival in various cancer types such as hepatocellular carcinoma (HCC), breast, lung or ovarian cancer. The multivariate analyses demonstrated that NCAPG, TNM, and Barcelona Clinic Liver Cancer (BCLC) staging were independent risk factors for mortality of patients with HCC. Moreover, functional and pathway enrichment analysis suggested that NCAPG was closely correlated with the pathways of cell cycle, cellular senescence, and mismatch repair. By weighted gene co-expression network analysis (WGCNA), we identified NCAPG as a hub gene in the turquoise module mostly related to the survival time of HCC samples. Conclusion To our knowledge, this study represents a comprehensive RNA-Seq analysis of several tumor types, revealing NCAPG as a promising molecular target. NCAPG overexpression may play important roles in carcinogenesis and progression of tumors via regulating tumor-related pathways, thereby broadening the understanding of the pathogenic mechanisms and highlighting the possibility of developing novel targeted therapeutics.