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微小染色体维持基因家族:肺鳞状细胞癌的潜在治疗靶点和预后生物标志物。

Minichromosome maintenance gene family: potential therapeutic targets and prognostic biomarkers for lung squamous cell carcinoma.

机构信息

Department of Pathology, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.

Departments of Ultrasound Imaging, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.

出版信息

Aging (Albany NY). 2022 Nov 28;14(22):9167-9185. doi: 10.18632/aging.204399.

Abstract

The minichromosome maintenance (MCM) gene family comprises of ten members with key roles in eukaryotic DNA replication and are associated with the occurrence and progression of many tumors. However, whether the MCM family contributes to lung squamous cell carcinoma (LUSC) is unclear. In this study, we performed bioinformatic analysis to identify the roles of MCM genes in patients with LUSC. We also evaluated their differential gene expression, prognostic correlation, DNA methylation, functional enrichment of genetic alterations, and immunomodulation. According to the Tumor Immune Estimation Resource database, the expression of MCM2-10 mRNA was elevated in LUSC tissues. According to the Gene Expression Profiling Interactive Analysis database, MCM2-8 and MCM10 were considerably upregulated in LUSC tissues, and protein levels of all MCMs were increased in LUSC tissues. In addition, among the MCM family members, the expression of MCM3 and MCM7 showed the strongest correlation with the prognoses of patients with LUSC. To clarify the role and mechanisms of the MCM family, Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment studies were performed. We detected a significant correlation between the expression patterns of MCM family members and infiltrating immune cells. In conclusion, our results improve the understanding of the aberrant expression of MCM family members in LUSC. These findings demonstrate the potential of the MCM family as therapeutic targets and biomarkers for the diagnosis and prognosis of LUSC.

摘要

微小染色体维持 (MCM) 基因家族由十个成员组成,在真核生物 DNA 复制中发挥关键作用,并与许多肿瘤的发生和进展有关。然而,MCM 家族是否参与肺鳞状细胞癌(LUSC)尚不清楚。在本研究中,我们进行了生物信息学分析,以确定 MCM 基因在 LUSC 患者中的作用。我们还评估了它们的差异基因表达、预后相关性、DNA 甲基化、遗传改变的功能富集和免疫调节。根据肿瘤免疫估计资源数据库,LUSC 组织中 MCM2-10 mRNA 的表达升高。根据基因表达谱交互分析数据库,MCM2-8 和 MCM10 在 LUSC 组织中显著上调,所有 MCM 的蛋白水平在 LUSC 组织中增加。此外,在 MCM 家族成员中,MCM3 和 MCM7 的表达与 LUSC 患者的预后相关性最强。为了阐明 MCM 家族的作用和机制,进行了京都基因与基因组百科全书和基因本体富集研究。我们检测到 MCM 家族成员表达模式与浸润免疫细胞之间存在显著相关性。总之,我们的研究结果提高了对 LUSC 中 MCM 家族成员异常表达的认识。这些发现表明 MCM 家族作为治疗靶点和 LUSC 诊断和预后的生物标志物的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10e7/9740372/a3583473a2b6/aging-14-204399-g001.jpg

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