Abstract
Minichromosome maintenance proteins (MCMs) are considered to be essential factors coupling DNA replication to both cell cycle progression and checkpoint regulation. Previous studies have shown that dysregulation of MCMs are implicated in tumorigenesis of lung cancer. However, the distinct expression/mutation patterns and prognostic values of MCMs in lung cancer have yet to be systematically elucidated. In the present study, we analyzed the transcriptional levels, mutations, and prognostic value of MCM1-10 in non-small cell lung cancer (NSCLC) patients using multiple bioinformatics tools, including ONCOMINE, GEPIA, Kaplan–Meier Plotter, cBioPortal, and GESA. The analysis results from GEPIA dataset showed that MCM2/4/10 was significantly high expressed in both lung adenocarcinoma (LUAD) and squamous cell lung carcinomas (LUSCs). Meanwhile, the expression levels of MCM2/4/6/7/8 were associated with advanced tumor stages. Subsequent survival analysis using the Kaplan–Meier Plotter indicated that high expression levels of MCM1/2/3/4/5/6/7/8/10 were associated with worse overall survival (OS), while high expression level of MCM9 predicted better OS in these patients. Furthermore, we experimentally validated overexpression of MCM2 and MCM4 in NSCLC, thus the results from this study support a view that they may serve as potential prospective biomarkers to identify high-risk subgroups of NSCLC patients.
Highlights
Lung cancer is an common but highly fatal malignancy worldwide, with a 5-year overall survival (OS) varying from 4–17% depending on the tumor stage and regional differences (Lewis et al, 2010)
Analyzed with the same Hou’s database, the mRNA level of MCM2 was upregulated in large cell lung carcinoma and lung adenocarcinoma (LUAD) patients with a fold change of 5.129 and 3.25, respectively
We found that MCM7 was highly expressed in LUAD, while MCM8/10 were overexpressed in large cell lung cancer and squamous cell lung carcinoma (LUSC), all of which negatively associated with patient’s OS
Summary
Lung cancer is an common but highly fatal malignancy worldwide, with a 5-year overall survival (OS) varying from 4–17% depending on the tumor stage and regional differences (Lewis et al, 2010). Lung cancer can be classified into small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). NSCLC accounts for 80% of total lung cancer cases, and can be further divided into lung adenocarcinoma (LUAD), squamous cell lung carcinoma (LUSC), and large cell lung carcinoma. Minichromosome maintenance proteins (MCMs), as a group of proteins responsible for minichromosome maintenance, play essential roles in initiation of DNA replication and cell proliferation (Forsburg, 2004). They are required for replication elongation, and implicated in cohesion, condensation, transcription, and recombination of DNA molecule (Forsburg, 2004). MCM2-7 binds to the origin part of replication at G1 phase, acting as the key regulatory components for DNA replication permission (Cannone et al, 2017)
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