微型染色体维持蛋白10在肝癌中的表达和预后价值及作用机制研究
Study on the expression,prognosis and mechanism of minichromosome maintenance protein 10 in hepatocellular carcinoma
贾锋宇 1王亮2
作者信息
- 1. 锦州医科大学,锦州 121000
- 2. 锦州医科大学附属第一医院普外科,锦州 121000
- 折叠
摘要
目的 分析微小染色体维持蛋白10(MCM10)在肝癌中的表达和预后预测价值及作用机制.方法 从癌症基因组图谱数据库获取肝细胞肝癌转录组数据和临床数据,应用秩和检验对肿瘤组织和癌旁组织的MCM10表达水平进行分析.Cox回归分析MCM10表达水平与肝细胞肝癌患者生存预后的关系.应用基因集富集分析(GSEA)对MCM10高、低表达组之间差异基因表达谱进行通路富集分析.应用细胞计数实验(CCK-8)测定MCM10基因敲低对肝癌细胞HepG2增殖能力的影响;采用蛋白免疫印迹法检测MCM10基因敲低后对细胞G1/S-特异性周期蛋白-D1(cyclin D1)表达的影响.结果 肝细胞肝癌中MCM10表达值为0.709±0.595,癌旁组织中MCM10表达值为0.077 ±0.094,差异有统计学意义(P＜0.0001).Cox回归分析显示MCM10高表达是肝细胞肝癌总生存期(HR=1.32,95％CI:1.19～1.48)和疾病特异性生存期(HR=1.40,95％CI:1.22～1.61)的危险因素和预后预测指标.GSEA分析表明差异基因主要富集在细胞周期、P53信号通路和细胞周期G1-S期正向调控等通路.CCK-8结果显示MCM10敲低能够抑制HepG2细胞增殖;蛋白免疫印迹分析进一步证实敲低MCM10表达可抑制HepG2细胞cyclin D1的表达.结论 MCM10高表达是肝细胞肝癌患者预后的风险因素,MCM10能够通过cyclin D1促进肝癌细胞增殖从而发挥促肝癌的作用.
Abstract
Objective To investigate the expression,prognostic value and mechanism of MCM10 in hepatocellular carcinoma(LIHC).Methods The transcriptome and clinical data of hepatocellular carcino-ma were obtained from The Cancer Genome Atlas database,and the rank sum test was used to analyze the expression level of MCM10 in tumor tissues and adjacent tissues.Cox regression analysis was used to analyze the relationship between MCM10 expression level and the survival prognosis of patients with hepatocellular carcinoma.Gene set enrichment analysis(GSEA)was utilized for pathway enrichment analysis between MCM10 high and low group gene expression profiles.The effect of MCM10 knockdown on the proliferation of HepG2 cells was determined by cell counting kit-8(CCK-8)cell viability assay.The effect of MCM10 knockdown on the expression of G1/S-specific cyclin D1 was detected by Western blot.Results The expression value of MCM10 in hepatocellular carcinoma was 0.709±0.595,and that in adjacent tissues was 0.077±0.094(P＜0.0 001).Cox regression analysis showed that high expression of MCM10 was a risk factor and prognostic predictor of overall survival(HR=1.32,95％CI:1.19～1.48)and disease-specific survival(HR=1.40,95％CI:1.22～1.61)in LIHC.GSEA analysis showed that the differentially expressed genes were mainly enriched in cell cycle,p53 signaling pathway and positive regulation of G1-S phase transition,et al.CCK-8 assay showed that MCM10 knockdown could inhibit the proliferation of HepG2 cells.Western blot analysis further confirmed that knockdown of MCM10 expression inhibited the expression of cyclin D1 in HepG2 cells.Conclusions MCM10 is a risk factor for the prognosis of patients with hepatocellular carcinoma,which can promote the proliferation of hepatoma cells through cyclin D1.
关键词
癌,肝细胞/微小染色体维持蛋白10/预后/基因集富集分析/细胞周期蛋白D1Key words
Carcinoma,hepatocellular/Minichromosome maintenance protein 10/Prognosis/Gene set enrichment analysis/Cyclin D1引用本文复制引用
基金项目
辽宁省自然科学基金(2020-MS-297)
出版年
2024
NETL
NSTL
万方数据