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全基因组分析微小染色体维持蛋白家族基因在肺腺癌患者中的临床意义和潜在分子机制。

Genome-wide investigation of the clinical significance and prospective molecular mechanism of minichromosome maintenance protein family genes in patients with Lung Adenocarcinoma.

机构信息

Department of Radiation Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, People's Republic of China.

Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, People's Republic of China.

出版信息

PLoS One. 2019 Jul 19;14(7):e0219467. doi: 10.1371/journal.pone.0219467. eCollection 2019.

Abstract

Our current study is to identify clinical significance of minichromosome maintenance (MCM) gene expression in Lung Adenocarcinoma (LUAD) using genome-wide RNA sequencing (RNA-seq) dataset and bioinformatics analysis tools. The biological function and potential process for function of the MCM1-10 were identified by multiple bioinformatics analysis tools. Clinical significance and molecular mechanism of the MCM1-10 were investigated by the RNA-seq dataset of LUAD from The Cancer Genome Atlas. Functional assessment substantiated involvement of MCM1-10 in cell cycle progression and DNA replication, and co-expressed with each other. We also observed that the MCM1-10 were dysregulation in LUAD tumor tissues, and may be have diagnostic implications in LUAD. Prognosis analysis in TCGA and KM plotter cohorts suggest that high abundance of MCM5, MCM8 and MCM4 notably correlated to poor LUAD overall survival. Mechanistic exploration of MCM4, MCM5, and MCM8 by gene set enrichment analysis suggests that these genes may influence the LUAD prognosis by regulating the cell cycle, DNA replication and other multiple biological processes and pathways. In comclusion, our study suggests that MCM1-10 can serve as diagnostic biomarkers for LUAD patients. Of them, MCM4, MCM5, and MCM8 may act as potential prognostic indicators for LUAD.

摘要

我们目前的研究旨在使用全基因组 RNA 测序 (RNA-seq) 数据集和生物信息学分析工具来确定微小染色体维持 (MCM) 基因表达在肺腺癌 (LUAD) 中的临床意义。通过多种生物信息学分析工具确定了 MCM1-10 的生物学功能和潜在功能过程。通过癌症基因组图谱 (TCGA) 的 LUAD RNA-seq 数据集研究了 MCM1-10 的临床意义和分子机制。功能评估证实了 MCM1-10 参与细胞周期进程和 DNA 复制,并相互共表达。我们还观察到 MCM1-10 在 LUAD 肿瘤组织中失调,并且可能对 LUAD 具有诊断意义。TCGA 和 KM plotter 队列的预后分析表明,MCM5、MCM8 和 MCM4 的高丰度与 LUAD 总生存期不良显著相关。通过基因集富集分析对 MCM4、MCM5 和 MCM8 的机制探索表明,这些基因可能通过调节细胞周期、DNA 复制和其他多个生物学过程和途径来影响 LUAD 的预后。总之,我们的研究表明 MCM1-10 可以作为 LUAD 患者的诊断生物标志物。其中,MCM4、MCM5 和 MCM8 可能作为 LUAD 的潜在预后指标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9e9/6641114/9acdd7736f2d/pone.0219467.g001.jpg

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