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人类癌症中微小染色体维持蛋白(MCMs)表达的泛癌多组学分析

Pan-Cancer Multi-Omics Analysis of Minichromosome Maintenance Proteins (MCMs) Expression in Human Cancers.

作者信息

Wang Lulu, Liu Xiaowei

机构信息

Department of General Practice, Yangpu Hospital, School of Medicine, Tongji University, 200090 Shanghai, China.

Department of Spinal Surgery, Shanghai East Hospital, School of Medicine, Tongji University, 200092 Shanghai, China.

出版信息

Front Biosci (Landmark Ed). 2023 Sep 27;28(9):230. doi: 10.31083/j.fbl2809230.

Abstract

BACKGROUND

Epigenetic modifications, such as transcription, DNA repair, and replication significantly influence tumour development. Aberrant gene expression and modifications can have a crucial impact on the initiation and progression of tumours. The minichromosome maintenance (MCM) protein family, which is responsible for DNA synthesis, plays a crucial role in tumorigenesis and chemotherapy resistance by regulating the cell cycle and DNA replication stress. Recent studies have shown that dysregulation of the MCMs can lead to these negative outcomes. This study aimed to examine the role of the MCM proteins in DNA synthesis in 33 types of cancers.

METHODS

Various public databases were used to examine the expression, methylation regulation, mutations, and functions of eight MCM proteins (MCM2-9) in pan-cancer. The study investigated the correlation between abnormal MCM expression and clinical outcomes, including prognosis and drug response. The microRNA-mRNA network upstream of the genes and the downstream signalling pathways were extensively investigated to determine the molecular mechanisms that drive tumour development.

RESULTS

The study found that the gene expressions differed depending on the type of cancer; high gene expression was linked to poor overall survival in most cancers. Additionally, gene expression was associated with various immunological features and drug sensitivity. These findings offer important insights for the development of targeted cancer therapies.

CONCLUSIONS

Altogether, this study reveals that the genes are differentially expressed across various cancers and are associated with clinical prognoses. These genes may influence the occurrence and development of tumours through several pathways, including the PI3K-AKT, PAS/MAPK and TSC/mTOR signalling pathways and immune-related pathways.

摘要

背景

表观遗传修饰,如转录、DNA修复和复制,对肿瘤发展有显著影响。异常的基因表达和修饰可对肿瘤的发生和进展产生关键影响。负责DNA合成的微小染色体维持(MCM)蛋白家族,通过调节细胞周期和DNA复制应激,在肿瘤发生和化疗耐药中起关键作用。最近的研究表明,MCMs的失调可导致这些负面结果。本研究旨在探讨MCM蛋白在33种癌症的DNA合成中的作用。

方法

使用各种公共数据库来研究泛癌中八种MCM蛋白(MCM2 - 9)的表达、甲基化调控、突变和功能。该研究调查了MCM异常表达与临床结果之间的相关性,包括预后和药物反应。广泛研究了基因上游的microRNA - mRNA网络和下游信号通路,以确定驱动肿瘤发展的分子机制。

结果

研究发现,基因表达因癌症类型而异;在大多数癌症中,高基因表达与较差的总生存期相关。此外,基因表达与各种免疫特征和药物敏感性相关。这些发现为靶向癌症治疗的发展提供了重要见解。

结论

总之,本研究表明基因在各种癌症中差异表达,并与临床预后相关。这些基因可能通过多种途径影响肿瘤的发生和发展,包括PI3K - AKT、PAS/MAPK和TSC/mTOR信号通路以及免疫相关途径。

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