The Expression and Prognostic Roles of MCMs in Pancreatic Cancer

PLoS One. 2016 Oct 3;11(10):e0164150. doi: 10.1371/journal.pone.0164150. eCollection 2016.

Abstract

Objectives: Minichromosome maintenance (MCM) proteins play important roles in DNA replication by interacting with other factors which participate in the regulation of DNA synthesis. Abnormal over-expression of MCMs was observed in numerous malignancies, such as colorectal cancer. However, the expression of MCMs in pancreatic cancer (PC) was less investigated so far. This study was designed to analyze the expression and prognostic roles of MCM1-10 in PC based on the data provided by The Cancer Genome Atlas (TCGA).

Methods: Pearson χ2 test was applied to evaluate the association of MCMs expression with clinicopathologic indicators, and biomarkers for tumor biological behaviors. Kaplan-Meier plots and log-rank tests were used to assess survival analysis, and univariate and multivariate Cox proportional hazard regression models were used to recognize independent prognostic factors.

Results: MCM1-10 were generally expressed in PC samples. The levels of some molecules were markedly correlated with that of biomarkers for S phase, proliferation, gemcitabine resistance. And part of these molecules over-expression was significantly associated with indicators of disease progression, such as depth of tumor invasion and lymph node metastasis. Furthermore, MCM2, 4, 6, 8, and 10 over-expression was remarkably associated with shorter disease free survival time, and MCM2, 4,8, and 10 over-expression was associated with shorter overall survival time. Further multivariate analysis suggested that MCM8 was an independent prognostic factor for PC.

Conclusion: MCMs abnormal over-expression was significantly associated with PC progression and prognosis. These molecules could be regarded as prognostic and therapeutic biomarkers for PC. The roles of MCMs may be vitally important and the underlying mechanisms need to be furtherinvestigated.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor
  • Computational Biology / methods
  • Databases, Factual
  • Female
  • Gene Expression*
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Minichromosome Maintenance Proteins / genetics*
  • Neoplasm Staging
  • Pancreatic Neoplasms / diagnosis
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / mortality*
  • Patient Outcome Assessment
  • Prognosis
  • Proportional Hazards Models

Substances

  • Biomarkers, Tumor
  • Minichromosome Maintenance Proteins

Grants and funding

Funded by grant numbers: 81170336 and 81272239, website: http://www.nsfc.gov.cn/, full name of the funding institutions: National Natural Science Foundation of China, authors who received the funding: Yi Miao. Dr. Yi Miao designed this study.