Xiao Cuicui, Gong Jiao, Jie Yusheng, Cao Jing, Chen Zhongcheng, Li Rong, Chong Yutian, Hu Bo, Zhang Qi
Cell-Gene Therapy Translational Medicine Research Center, Key Laboratory of Liver Disease of Guangdong Province, Guangzhou, China.
Department of Laboratory Medicine, Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Front Pharmacol. 2020 Apr 2;11:387. doi: 10.3389/fphar.2020.00387. eCollection 2020.
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.
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.
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 regulating tumor-related pathways, thereby broadening the understanding of the pathogenic mechanisms and highlighting the possibility of developing novel targeted therapeutics.
随着CRISPR-Cas9基因组编辑工具在基因治疗中的出现,鉴定异常表达基因在各种癌症类型中具有重要价值。因为大量患者可能从分子靶向基因治疗中受益。本研究的目的是鉴定各种癌症类型中异常表达的基因,分析潜在机制及其与生存结果的相关性。
在癌症基因组图谱(TCGA)数据库中,NCAPG高表达,该数据库包含来自16种癌症类型的6647个癌症和647个正常组织样本的转录组。此外,在16种肿瘤类型的蛋白质水平上也观察到预测的NCAPG过表达率。重要的是,高NCAPG水平与多种癌症类型(如肝细胞癌(HCC)、乳腺癌、肺癌或卵巢癌)的不良生存显著相关。多变量分析表明,NCAPG、TNM和巴塞罗那临床肝癌(BCLC)分期是HCC患者死亡的独立危险因素。此外,功能和通路富集分析表明,NCAPG与细胞周期、细胞衰老和错配修复通路密切相关。通过加权基因共表达网络分析(WGCNA),我们将NCAPG鉴定为绿松石模块中的一个枢纽基因,该模块主要与HCC样本的生存时间相关。
据我们所知,本研究代表了对几种肿瘤类型的全面RNA测序分析,揭示了NCAPG是一个有前景的分子靶点。NCAPG过表达可能在肿瘤的发生和进展中起重要作用,调节肿瘤相关通路,从而拓宽对致病机制的理解,并突出开发新型靶向治疗药物的可能性。