Pei Li-Peng, Zhang Yun-Zheng, Li Guang-Ying, Sun Jing-Li
Department of Obstetrics and Gynecology, General Hospital of Northern Theater Command, Shenyang, China.
Front Genet. 2022 Jun 3;13:890591. doi: 10.3389/fgene.2022.890591. eCollection 2022.
Mini chromosome maintenance protein 4 (MCM4) belongs to the family of mini chromosome maintenance proteins (MCMs) that plays a crucial role in DNA replication and cell cycle regulation. Given that MCM4 has been reported to be aberrantly expressed in a variety of tumor tissues, and is strongly associated with poor patient prognosis, it has rarely been reported in uterine corpus endometrial carcinoma (UCEC). We explored the role of MCM4 in UCEC through multi-omics analysis, including gene expression levels, survival prognosis, the biological function of interacting proteins, immune infiltration, and diagnostic value. Finally, these results were confirmed by biological experiments. MCM4 was highly expressed in various malignancies including UCEC compared to normal samples and was associated with poor prognosis in patients with UCEC [including OS (HR = 1.74, = 0.009), PFI (HR = 1.73, = 0.002), PFI (HR = 2.23, = 0.003)]. In the Cox regression analysis, MCM4 was an independent prognostic biomarker. Further studies showed those interacting proteins of MCM4 were enriched in DNA repair and cell cycle. Moreover, high expression of MCM4 was accompanied by lower infiltration of immune cells such as Treg cells and B cells. The distribution of MCM4 expression in molecular and immune subtypes was significantly different ( < 0.05), with high expression in the copynumber high (CN_HIGH) molecular subtype and the IFN-gamma dominant (C2) immune subtype. RT-qPCR and immunohistochemistry results also showed that MCM4 expression was significantly upregulated in endometrial cancer tissues and negatively correlated with patient prognosis ( < 0.05). Subsequent biological experiments confirmed that MCM4 promoted cell growth and invasion and inhibited apoptosis . Therefore, MCM4 could be a new potential biomarker for UCEC.
微小染色体维持蛋白4(MCM4)属于微小染色体维持蛋白(MCMs)家族,在DNA复制和细胞周期调控中起关键作用。鉴于已有报道称MCM4在多种肿瘤组织中异常表达,且与患者预后不良密切相关,但其在子宫体子宫内膜癌(UCEC)中的报道较少。我们通过多组学分析,包括基因表达水平、生存预后、相互作用蛋白的生物学功能、免疫浸润和诊断价值,探讨了MCM4在UCEC中的作用。最后,通过生物学实验证实了这些结果。与正常样本相比,MCM4在包括UCEC在内的各种恶性肿瘤中高表达,且与UCEC患者的预后不良相关[包括总生存期(HR = 1.74,P = 0.009)、无进展生存期(HR = 1.73,P = 0.002)、无病生存期(HR = 2.23,P = 0.003)]。在Cox回归分析中,MCM4是一个独立的预后生物标志物。进一步研究表明,MCM4的相互作用蛋白富集于DNA修复和细胞周期。此外,MCM4的高表达伴随着Treg细胞和B细胞等免疫细胞浸润的减少。MCM4表达在分子和免疫亚型中的分布存在显著差异(P < 0.05),在拷贝数高(CN_HIGH)分子亚型和干扰素-γ主导(C2)免疫亚型中高表达。RT-qPCR和免疫组织化学结果也显示,MCM4表达在子宫内膜癌组织中显著上调,且与患者预后呈负相关(P < 0.05)。随后的生物学实验证实,MCM4促进细胞生长和侵袭并抑制细胞凋亡。因此,MCM4可能是UCEC的一种新的潜在生物标志物。