Elevated mRNA Levels of AURKA, CDC20 and TPX2 are associated with poor prognosis of smoking related lung adenocarcinoma using bioinformatics analysis

Int J Med Sci. 2018 Nov 5;15(14):1676-1685. doi: 10.7150/ijms.28728. eCollection 2018.

Abstract

Background and aim: Adenocarcinoma is a very common pathological subtype for lung cancer. We aimed to identify the gene signature associated with the prognosis of smoking related lung adenocarcinoma using bioinformatics analysis. Methods: A total of five gene expression profiles (GSE31210, GSE32863, GSE40791, GSE43458 and GSE75037) have been identified from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were analyzed using GEO2R software and functional and pathway enrichment analysis. Furthermore, the overall survival (OS) and recurrence-free survival (RFS) have been validated using an independent cohort from the Cancer Genome Atlas (TCGA) database. Results: We identified a total of 58 DEGs which mainly enriched in ECM-receptor interaction, platelet activation and PPAR signaling pathway. Then according to the enrichment analysis results, we selected three genes (AURKA, CDC20 and TPX2) for their roles in regulating tumor cell cycle and cell division. The results showed that the hazard ratio (HR) of the mRNA expression of AURKA for OS was 1.588 with (1.127-2.237) 95% confidence interval (CI) (P=0.009). The mRNA levels of CDC20 (HR 1.530, 95% CI 1.086-2.115, P=0.016) and TPX2 (HR 1.777, 95%CI 1.262-2.503, P=0.001) were also significantly associated with the OS. Expression of these three genes were not associated with RFS, suggesting that there might be many factors affect RFS. Conclusion: The mRNA signature of AURKA, CDC20 and TPX2 were potential biomarkers for predicting poor prognosis of smoking related lung adenocarcinoma.

Keywords: Kaplan-Meier analysis; biomarkers; differentially expressed genes; gene ontology; lung adenocarcinoma.

MeSH terms

  • Adenocarcinoma of Lung / etiology
  • Adenocarcinoma of Lung / genetics
  • Adenocarcinoma of Lung / mortality
  • Adenocarcinoma of Lung / pathology*
  • Aged
  • Aurora Kinase A / analysis*
  • Aurora Kinase A / genetics
  • Biomarkers, Tumor / analysis*
  • Biomarkers, Tumor / genetics
  • Cdc20 Proteins / analysis*
  • Cdc20 Proteins / genetics
  • Cell Cycle Proteins / analysis*
  • Cell Cycle Proteins / genetics
  • Computational Biology
  • Datasets as Topic
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kaplan-Meier Estimate
  • Lung Neoplasms / etiology
  • Lung Neoplasms / genetics
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology*
  • Male
  • Microtubule-Associated Proteins / analysis*
  • Microtubule-Associated Proteins / genetics
  • Middle Aged
  • Nuclear Proteins / analysis*
  • Nuclear Proteins / genetics
  • Prognosis
  • RNA, Messenger / analysis
  • Smoking / adverse effects
  • Transcriptome / genetics

Substances

  • Biomarkers, Tumor
  • Cdc20 Proteins
  • Cell Cycle Proteins
  • Microtubule-Associated Proteins
  • Nuclear Proteins
  • RNA, Messenger
  • TPX2 protein, human
  • CDC20 protein, human
  • AURKA protein, human
  • Aurora Kinase A