Huang Qian-Rong, Jiang Qian, Tan Ju-Yuan, Nong Ren-Bao, Yan Jun, Yang Xia-Wei, Mo Li-Gen, Ling Guo-Yuan, Deng Teng, Gong Yi-Zhen
Department of Neurosurgery, Guangxi Medical University Cancer Hospital, Nanning, China.
Guangxi Medical University, Nanning, China.
Front Pharmacol. 2024 Apr 18;15:1390615. doi: 10.3389/fphar.2024.1390615. eCollection 2024.
Previous studies have shown that MCM3 plays a key role in initiating DNA replication. However, the mechanism of MCM3 function in most cancers is still unknown. The aim of our study was to explore the expression, prognostic role, and immunological characteristics of MCM3 across cancers. We explored the expression pattern of MCM3 across cancers. We subsequently explored the prognostic value of MCM3 expression by using univariate Cox regression analysis. Spearman correlation analysis was performed to determine the correlations between MCM3 and immune-related characteristics, mismatching repair (MMR) signatures, RNA modulator genes, cancer stemness, programmed cell death (PCD) gene expression, tumour mutation burden (TMB), microsatellite instability (MSI), and neoantigen levels. The role of MCM3 in predicting the response to immune checkpoint blockade (ICB) therapy was further evaluated in four immunotherapy cohorts. Single-cell data from CancerSEA were analysed to assess the biological functions associated with MCM3 in 14 cancers. The clinical correlation and independent prognostic significance of MCM3 were further analysed in the TCGA and CGGA lower-grade glioma (LGG) cohorts, and a prognostic nomogram was constructed. Immunohistochemistry in a clinical cohort was utilized to validate the prognostic utility of MCM3 expression in LGG. MCM3 expression was upregulated in most tumours and strongly associated with patient outcomes in many cancers. Correlation analyses demonstrated that MCM3 expression was closely linked to immune cell infiltration, immune checkpoints, MMR genes, RNA modulator genes, cancer stemness, PCD genes and the TMB in most tumours. There was an obvious difference in outcomes between patients with high MCM3 expression and those with low MCM3 expression in the 4 ICB treatment cohorts. Single-cell analysis indicated that MCM3 was mainly linked to the cell cycle, DNA damage and DNA repair. The expression of MCM3 was associated with the clinical features of LGG patients and was an independent prognostic indicator. Finally, the prognostic significance of MCM3 in LGG was validated in a clinical cohort. Our study suggested that MCM3 can be used as a potential prognostic marker for cancers and may be associated with tumour immunity. In addition, MCM3 is a promising predictor of immunotherapy responses.
先前的研究表明，MCM3在启动DNA复制过程中起关键作用。然而，MCM3在大多数癌症中的功能机制仍不清楚。我们研究的目的是探索MCM3在各种癌症中的表达、预后作用及免疫学特征。我们探究了MCM3在各种癌症中的表达模式。随后，我们使用单因素Cox回归分析探究了MCM3表达的预后价值。进行Spearman相关性分析以确定MCM3与免疫相关特征、错配修复（MMR）特征、RNA调节基因、癌症干性、程序性细胞死亡（PCD）基因表达、肿瘤突变负荷（TMB）、微卫星不稳定性（MSI）和新抗原水平之间的相关性。在四个免疫治疗队列中进一步评估了MCM3在预测免疫检查点阻断（ICB）治疗反应中的作用。分析了来自CancerSEA的单细胞数据，以评估MCM3在14种癌症中的生物学功能。在TCGA和CGGA低级别胶质瘤（LGG）队列中进一步分析了MCM3的临床相关性和独立预后意义，并构建了预后列线图。利用一个临床队列中的免疫组织化学方法验证MCM3表达在LGG中的预后效用。MCM3表达在大多数肿瘤中上调，且在许多癌症中与患者预后密切相关。相关性分析表明，在大多数肿瘤中，MCM3表达与免疫细胞浸润、免疫检查点、MMR基因、RNA调节基因、癌症干性、PCD基因和TMB密切相关。在4个ICB治疗队列中，MCM3高表达患者与低表达患者的预后存在明显差异。单细胞分析表明，MCM3主要与细胞周期、DNA损伤和DNA修复相关。MCM3的表达与LGG患者的临床特征相关，是一个独立的预后指标。最后，在一个临床队列中验证了MCM3在LGG中的预后意义。我们的研究表明，MCM3可作为癌症潜在的预后标志物，可能与肿瘤免疫相关。此外，MCM3是免疫治疗反应的一个有前景的预测指标。
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