Scientific Research Center, Guilin Medical University, Guilin, Guangxi, China; Pharmaceutical College, Guangxi Medical University, Nanning, Guangxi, China.
Department of Clinical Laboratory, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
Biomed Pharmacother. 2020 Jul;127:110171. doi: 10.1016/j.biopha.2020.110171. Epub 2020 May 8.
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.
微小染色体维持复合物组件 6(MCM6)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 MCM6 对中国南方壮族人群 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 MCM6 的全局 mRNA 水平外,还分析了 MCM6 mRNA 水平与临床病理特征之间的关系。高 MCM6 水平与高甲胎蛋白(AFP)(血清中>20ng/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 MCM6 与较差的预后相关(P<0.01)。此外,通过定量聚合酶链反应(qPCR)、western blot 和免疫组织化学(IHC)检测广西壮族人群中 MCM6 的 mRNA 和蛋白表达。结果表明,壮族 HCC 人群中 MCM6 水平上调。较高的 MCM6 蛋白水平与更大的肿瘤大小(>5cm)(P=0.038)和晚期临床分期(III+IV)(p=0.023)相关。MCM6 及其相互作用蛋白(CDT1、WEE1、TRIM28 和 MKI67)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。基于具有模块筛选的蛋白质-蛋白质相互作用(PPI)网络,通过热点分析进行蛋白质对接,进一步研究了 MCM6 与其潜在相互作用蛋白之间的相互作用。此外,MCM6 及其相互作用蛋白的 ROC 算法组合结果表明,组合生物标志物分析比单一 MCM6 测试具有更好的 HCC 诊断能力。MCM6 和 TRIM28 的组合更适合广西壮族人群。总体而言,本研究表明 MCM6 在 HCC 的生长中起重要作用。MCM6 可能是诊断 HCC 的最佳生物标志物,也是壮族人群 HCC 治疗的潜在分子靶点。