Zhen Yu, Fu Hanlin, Si Lulu, Lai Tianjiao, Chu Danxia, Guo Ruixia
Department of Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Medical Key Laboratory for Prevention and Treatment of Malignant Gynecological Tumor, Henan Province, China.
Comb Chem High Throughput Screen. 2023;26(4):815-825. doi: 10.2174/1386207325666220705111240.
Minichromosome maintenance (MCM) has been demonstrated to be involved in tumorigenesis and pathogenesis of many cancer types. However, the role of MCMs in endometrial cancer (EC) has not been elucidated.
We first employed GEPIA, cBioPortal, and R software to perform the differential expression analysis, survival analysis, and gene alteration analysis of the MCMs family. Then, GSE17025 and GSE63678 datasets and CTPAC were used to verify the mRNA and protein expression levels of MCM4. In addition, the internal mechanism of the MCM4 was investigated by comparing MCM4 expression-correlated differentially expressed genes (DEGs) from GEPIA and MCM4-interacted genes from STRING. Last, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to identify MCM4-related biological processes.
Compared with normal tissues, only MCM2 and MCM4 expression were significantly upregulated in EC tissues. High expression of MCM4 was related to worse clinicopathological features and poor prognosis in EC cohorts. Additionally, a certain degree of gene alterations in the MCM2-7 gene was observed. By comparing MCM4 expression-correlated DEGs and MCM4- interacted genes, six genes were obtained: SSRP1, ORC1, GINS1, CDK2, DBF4 and GINS3. Functional enrichment analysis suggested that MCM4 may be involved in regulating the biological processes of DNA replication and the p53 signaling pathway.
This was the first comprehensive study to disclose the biological effects of MCMs in EC, indicating that MCM4 could be used as a new prognostic biomarker and potential therapeutic target for EC.
微小染色体维持蛋白(MCM)已被证明参与多种癌症类型的肿瘤发生和发病机制。然而,MCM在子宫内膜癌(EC)中的作用尚未阐明。
我们首先使用GEPIA、cBioPortal和R软件对MCM家族进行差异表达分析、生存分析和基因改变分析。然后,使用GSE17025和GSE63678数据集以及CTPAC来验证MCM4的mRNA和蛋白表达水平。此外,通过比较GEPIA中与MCM4表达相关的差异表达基因(DEG)和STRING中与MCM4相互作用的基因,研究了MCM4的内在机制。最后,进行基因本体论和京都基因与基因组百科全书(KEGG)通路分析,以确定与MCM4相关的生物学过程。
与正常组织相比,EC组织中仅MCM2和MCM4表达显著上调。MCM4的高表达与EC队列中较差的临床病理特征和不良预后相关。此外,观察到MCM2 - 7基因存在一定程度的基因改变。通过比较与MCM4表达相关的DEG和与MCM4相互作用的基因,获得了六个基因:SSRP1、ORC1、GINS1、CDK2、DBF4和GINS3。功能富集分析表明,MCM4可能参与调节DNA复制和p53信号通路的生物学过程。
这是首次全面研究揭示MCM在EC中的生物学效应,表明MCM4可作为EC的新的预后生物标志物和潜在治疗靶点。