Significant Role of MCM10 in Lung Adenocarcinoma: Promote Viability and Migration

Abstract

Background: Lung cancer is one of the most common cancer in the world, the role of minichromosome maintenance 10 (MCM10) in lung adenocarcinoma (ADC) is still unknown. Methods: Using TCGA (The Cancer Genome Atlas) database, MCM10 RNA-seq and patients’ clinicopathological characteristics were analyzed. The nomogram and Time-dependent area under the curve (AUC) were built from analysis of multivariate Cox regression model in TCGA database. In our patient cohort, the expression of MCM10 in gene and protein were detected, functional studies were further explored. Moreover, Gene Set Enrichment Analysis (GSEA) was performed using TCGA database.Results: In TCGA database and our patient cohort, MCM10 expression was higher in tumor tissues than normal tissues. Overall survival (OS) status revealed that high MCM10 group was poorer than low MCM10 group in TCGA database (p=0.0212) and our patient cohort (p=0.0391). Patients with higher MCM10 expression displayed shorter progression free survival (PFS) time in our patient cohort (p=0.0323). MCM10 could be a diagnostic marker due to receiver operating characteristic (ROC) curve in TCGA database (p<0.0001) and our patient cohort (p=0.0048). Univariate and multivariate cox analysis demonstrated that MCM10 was an independent prognosticator for ADC. The nomogram model combined MCM10 expression, age and pathologic stage could predict the probability of 1108 days OS and it was assessed by C-index and calibration curve in TCGA database. Time-dependent AUC showed this model in predicting OS probability was particularly effective in earlier patients. Silence of MCM10 inhibited the cell proliferation, induced the G0/G1 phase arrest in cell cycle, promoted apoptosis and decreased migration in vitro. GSEA identified that higher expression of MCM10 was positively correlated with cellular mitosis, cell cycle, chromatin assembly, DNA biosynthetic process and DNA replication. Conclusion: Our study reveals that MCM10 plays a crucial role and could be an important marker for prognosis in AD