The impact of MCM6 on hepatocellular carcinoma in a Southern Chinese Zhuang population
The impact of MCM6 on hepatocellular carcinoma in a Southern Chinese Zhuang population
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MCM6 对中国南方壮族人群肝癌的影响
DOI：
10.1016/j.biopha.2020.110171
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发表时间：
2020-07-01
影响因子：
7.5
通讯作者：
Yang, Xiaoli
中科院分区：
文献类型：
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作者：
Jia, Wenxian;Xie, Li;Yang, Xiaoli
微小染色体维持复合物6（MCM 6）参与肝细胞癌（HCC）的发生。由于其对不同人群的影响尚不清楚，本研究调查了中国南方壮族人群中MCM 6对HCC的影响。除了基于癌症基因组图谱数据库（TCGA）和基因表达综合数据库（GEO）评估MCM 6的总体mRNA水平外，还分析了MCM 6 mRNA水平与临床病理学特征之间的关联。高MCM 6水平与高甲胎蛋白（AFP）（血清> 20 ng/mL）（P < 0.0001）和晚期临床分期（III + IV）（P < 0.001）相关。在这些数据库中，较高的MCM 6与较差的结局相关（P < 0.01）。采用定量聚合酶链反应（qPCR）、免疫印迹和免疫组织化学（IHC）方法检测广西壮族人群MCM 6的mRNA和蛋白表达。结果显示，壮族肝癌患者MCM 6表达水平上调。较高的MCM 6蛋白水平与较大的肿瘤大小（> 5cm）（P = 0.038）和晚期临床分期（III + IV）（p = 0.023）相关。对MCM 6及其相互作用蛋白（CDT 1、WEE 1、TRIM 28和MKI 67）的生物信息学富集分析表明，这些复合物除了参与细胞周期过程外，还可能参与蛋白结合、复制前复合物组装和核代谢。在蛋白质相互作用（PPI）网络的基础上，通过蛋白质对接和热点分析，进一步研究了MCM 6与其潜在相互作用蛋白的相互作用.此外，结合MCM 6及其相互作用蛋白的ROC的算法的结果表明，组合生物标志物分析比单一MCM 6测试具有更好的HCC诊断能力。MCM 6与TRIM 28的组合更适合广西壮族群体。总的来说，我们的研究表明，MCM 6在HCC的生长中起着重要作用。MCM 6可能是诊断壮族人群肝癌的最佳生物标志物，也可能成为壮族人群肝癌治疗的潜在分子靶点。
Minichromosome maintenance complex component 6 (MCM6) is involved in tumorigenesis of hepatocellular carcinoma (HCC). Because its effect on different populations remains unclear, this study investigated the impact of MCM6 on HCC in Southern Chinese Zhuang population. In addition to assessing the global mRNA levels of MCM6 based on The Cancer Genome Atlas database (TCGA) and The Gene Expression Omnibus database (GEO), associations between MCM6 mRNA levels and clinicopathological features were analyzed. High MCM6 levels were associated with high alpha-fetoprotein (AFP) (> 20 ng/mL in serum) (P < 0.0001) and advanced clinical stage (III + IV) (P < 0.001). Higher MCM6 was associated with poorer outcomes (P < 0.01) in these databases. Furthermore, the mRNA and protein expression of MCM6 in the Guangxi Zhuang population was detected by quantitative polymerase chain reaction (qPCR), western blot, and immunohistochemistry (IHC). The results showed that MCM6 levels were up-regulated in the Zhuang population with HCC. Higher MCM6 protein levels were correlated with larger tumor size (> 5 cm) (P = 0.038) and advanced clinical stage (III + IV) (p = 0.023). Bioinformatic enrichment analysis of MCM6 and its interacting proteins (CDT1, WEE1, TRIM28 and MKI67) suggested that in addition to being involved in the cell cycle process, these complexes could also be involved in protein binding, pre-replication complex assemble, and nucleus metabolism. Based on the protein-protein interaction (PPI) network with module screen, the interactions between MCM6 and its potential interacting proteins were further studied through protein docking with hot spot analysis. Additionally, the results of the algorithms combining the ROC of MCM6 and its interacting proteins showed that combination biomarker analysis has better HCC diagnosis ability than the single MCM6 test. The combination of MCM6 and TRIM28 was more suitable for the Guangxi Zhuang population. Overall, our study suggests that MCM6 plays an important role in the growth of HCC. MCM6 could be an optimal biomarker for diagnosing HCC and a potential molecular target for HCC therapy in the Zhuang population.