GTSE1, CDC20, PCNA, and MCM6 Synergistically Affect Regulations in Cell Cycle and Indicate Poor Prognosis in Liver Cancer

Anal Cell Pathol (Amst). 2019 Dec 30:2019:1038069. doi: 10.1155/2019/1038069. eCollection 2019.

Abstract

GTSE1 is well correlated with tumor progression; however, little is known regarding its role in liver cancer prognosis. By analyzing the hepatocellular carcinoma (HCC) datasets in GEO and TCGA databases, we showed that high expression of GTSE1 was correlated with advanced pathologic stage and poor prognosis of HCC patients. To investigate underlying molecular mechanism, we generated GTSE1 knockdown HCC cell line and explored the effects of GTSE1 deficiency in cell growth. Between GTSE1 knockdown and wild-type HCC cells, we identified 979 differentially expressed genes (520 downregulated and 459 upregulated genes) in the analysis of microarray-based gene expression profiling. Functional enrichment analysis of DEGs suggested that S phase was dysregulated without GTSE1 expression, which was further verified from flow cytometry analysis. Moreover, three other DEGs: CDC20, PCNA, and MCM6, were also found contributing to GTSE1-related cell cycle arrest and to be associated with poor overall survival of HCC patients. In conclusion, GTSE1, together with CDC20, PCNA, and MCM6, may synergistically promote adverse prognosis in HCC by activating cell cycle. Genes like GTSE1, CDC20, PCNA, and MCM6 may be promising prognostic molecular biomarkers in liver cancer.

MeSH terms

  • Adult
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / pathology
  • Cdc20 Proteins / genetics
  • Cdc20 Proteins / metabolism*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Databases, Nucleic Acid
  • Gene Expression Regulation, Neoplastic
  • Gene Ontology
  • Humans
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / pathology
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism*
  • Minichromosome Maintenance Complex Component 6 / genetics
  • Minichromosome Maintenance Complex Component 6 / metabolism*
  • Prognosis
  • Proliferating Cell Nuclear Antigen / genetics
  • Proliferating Cell Nuclear Antigen / metabolism*
  • S Phase Cell Cycle Checkpoints / genetics*
  • Tissue Array Analysis
  • Up-Regulation

Substances

  • Biomarkers, Tumor
  • Cdc20 Proteins
  • GTSE1 protein, human
  • Microtubule-Associated Proteins
  • PCNA protein, human
  • Proliferating Cell Nuclear Antigen
  • CDC20 protein, human
  • MCM6 protein, human
  • Minichromosome Maintenance Complex Component 6