Strong Correlation between the Expression of CHEK1 and Clinicopathological Features of Patients with Multiple Myeloma

Crit Rev Eukaryot Gene Expr. 2020;30(4):349-357. doi: 10.1615/CritRevEukaryotGeneExpr.2020027084.

Abstract

Multiple myeloma (MM) is one of the most common malignancies, and the clinical outcome of patients with MM remains poor. Our objective is to screen biomarkers correlated with clinicopathological features and survival of patients with MM. A gene co-expression network was constructed to screen hub genes related to the three stages in the International Staging System (ISS) of MM. Functional analysis and protein-protein interaction analysis of the hub genes was performed. CHEK1, a gene most related to the ISS stages of MM, was selected for further clinical validation. A total of 780 hub genes correlated with ISS stages of MM were identified. Functional enrichment analysis of hub genes suggested that these genes were mostly enriched in several gene ontology (GO) terms and pathways from the Kyoto Encyclopedia of Genes and Genomes (KEGG) that were involved in cell proliferation and immune response. Expression of the gene for the protein checkpoint kinase I (CHEK1) was increased in MM cells from newly diagnosed patients (P = 0.0304) and relapsed patients (P = 0.0002) as compared to normal plasma cells. Meanwhile, CHEK1 was increased more in MM patients with stage II disease (P = 0.0321) and stage III disease (P = 0.0076) than in those with stage I disease. Survival analysis indicated that MM patients in the group characterized by low CHEK1 expression were associated with better clinical outcomes in terms of time to progression, event-free survival, and overall survival. High expression of CHEK1 predicted poor clinical characteristics of MM patient, and our results indicate that it can be considered a biomarker for the diagnosis of MM.

Publication types

  • Review

MeSH terms

  • Biomarkers, Tumor / genetics
  • Checkpoint Kinase 1 / genetics*
  • Humans
  • Multiple Myeloma / genetics*
  • Multiple Myeloma / pathology
  • Survival Analysis

Substances

  • Biomarkers, Tumor
  • CHEK1 protein, human
  • Checkpoint Kinase 1