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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma of Lung / genetics*
  • Adenocarcinoma of Lung / mortality
  • Cell Cycle
  • Cell Cycle Proteins / genetics
  • Cluster Analysis
  • Computational Biology
  • DNA Repair
  • DNA Replication
  • Databases, Factual
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Genome, Human
  • Genome-Wide Association Study*
  • Humans
  • Kaplan-Meier Estimate
  • Lung
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / mortality
  • Minichromosome Maintenance Complex Component 4 / genetics
  • Minichromosome Maintenance Proteins / genetics*
  • Prognosis
  • ROC Curve
  • Signal Transduction

Substances

  • Cell Cycle Proteins
  • MCM5 protein, human
  • MCM4 protein, human
  • MCM8 protein, human
  • Minichromosome Maintenance Complex Component 4
  • Minichromosome Maintenance Proteins

Grants and funding

This work was supported by grants from the National Natural Science Foundation of China (grant nos. 81460460, 81360405 and 81760542), the Foundation of Sharing Project Based on Tumor Precise Radiotherapy (grant no. ZY18076006) and the Research Foundation of the Science and Technology Department of Guangxi Province, China (grant nos. 2016GXNSFAA380252).