Department of Pathology, First Affiliated Hospital of Guangxi Medical University, Guangxi Zhuang Autonomous Region, PR China.
Guangxi key Laboratory of Enhanced Recovery after Surgery for Gastrointestinal Cancer, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, PR China.
Ann Med. 2024 Dec;56(1):2405879. doi: 10.1080/07853890.2024.2405879. Epub 2024 Sep 23.
Minichromosome maintenance complex component 3 (MCM3) plays a key role in various tumours. However, it remains largely unknown what the specific role and clinical significance of MCM3 in pancreatic adenocarcinoma (PAAD) are.
We integrated high-throughput data from PAAD worldwide to analyse the expression level of MCM3 mRNA. We used immunohistochemistry to analyse MCM3 protein expression levels in 145 cases in the PAAD group and 29 cases in the non-PAAD group. We also mainly analysed the necessity of MCM3 for PAAD growth based on CRISPR screen data. In addition, we used enrichment analysis and protein-protein interaction networks to explore the molecular mechanism of MCM3 in PAAD. We also analysed the correlation between MCM3 expression, components of the immune microenvironment in PAAD tissue and clinical prognosis.
In PAAD, we observed for the first time that MCM3 was significantly highly expressed at both the mRNA (SMD = 0.67, 95% CI: 0.38 ∼ 0.96) and the protein level ( < 0.05). The mRNA (AUC = 0.78, 95% CI: 0.74 ∼ 0.81; sensitivity = 0.66, 95% CI: 0.55 ∼ 0.76; specificity = 0.76, 95% CI: 0.67 ∼ 0.84) and protein (AUC = 0.929) expression levels of MCM3 had a good ability to distinguish between PAAD and non-PAAD tissue. There was heterogeneity reflected by the differential expression of MCM3 protein in PAAD cells. MCM3 played an essential role in PAAD growth, through abnormal DNA replication, p53 signalling and cell cycle checkpoints. PAAD with high MCM3 expression was sensitive to c-75, brivanib, flavopiridol and VNLG/124 drugs, with stable molecular docking models.
MCM3 is likely to be a critical element in promoting the initiation and growth of PAAD. Flavopiridol may exert its anti-PAAD effect through the interaction between MCM3, classic CDK1 targets in the cell cycle checkpoint and p53 pathway as well as related molecules in other pathways.
微小染色体维持复合物成分 3（MCM3）在各种肿瘤中发挥关键作用。然而，MCM3 在胰腺导管腺癌（PAAD）中的具体作用和临床意义在很大程度上仍不清楚。
我们整合了来自全球 PAAD 的高通量数据来分析 MCM3 mRNA 的表达水平。我们使用免疫组织化学分析了 145 例 PAAD 组和 29 例非 PAAD 组中 MCM3 蛋白的表达水平。我们还主要基于 CRISPR 筛选数据来分析 MCM3 对 PAAD 生长的必要性。此外，我们使用富集分析和蛋白质-蛋白质相互作用网络来探索 MCM3 在 PAAD 中的分子机制。我们还分析了 MCM3 表达与 PAAD 组织中免疫微环境成分之间的相关性以及与临床预后的关系。
在 PAAD 中，我们首次观察到 MCM3 在 mRNA（SMD = 0.67，95%CI：0.38∼0.96）和蛋白水平上均显著高表达（<0.05）。MCM3 的 mRNA（AUC = 0.78，95%CI：0.74∼0.81；灵敏度 = 0.66，95%CI：0.55∼0.76；特异性 = 0.76，95%CI：0.67∼0.84）和蛋白（AUC = 0.929）表达水平具有良好的区分 PAAD 和非 PAAD 组织的能力。MCM3 蛋白在 PAAD 细胞中的差异表达反映出异质性。MCM3 在 PAAD 生长中发挥重要作用，通过异常的 DNA 复制、p53 信号和细胞周期检查点。高 MCM3 表达的 PAAD 对 c-75、brivanib、flavopiridol 和 VNLG/124 药物敏感，具有稳定的分子对接模型。
MCM3 可能是促进 PAAD 起始和生长的关键因素。flavopiridol 可能通过 MCM3 与细胞周期检查点中的经典 CDK1 靶标以及 p53 途径以及其他途径中的相关分子之间的相互作用发挥其抗 PAAD 作用。
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