Expression of Cancer Stem Cell-associated DKK1 mRNA Serves as Prognostic Marker for Hepatocellular Carcinoma

Anticancer Res. 2017 Sep;37(9):4881-4888. doi: 10.21873/anticanres.11897.

Abstract

Background/aim: Cancer stem cells (CSCs) are associated with prognosis of hepatocellular carcinoma (HCC). In our previous study, we created cDNA microarray databases on the CSC population of human HuH7 cells. In the present study, we identified genes that might serve as prognostic markers of HCC by employing existing databases.

Materials and methods: Expressions of glutathione S-transferase pi 1 (GSTP1), lysozyme (LYZ), C-X-C motif chemokine ligand 5 (CXCL5), interleukin-8 (IL8) and dickkopf WNT signaling pathway inhibitor 1 (DKK1), the five most highly expressed genes in the CSC cDNA microarray databases, were examined in 99 patients with HCC by real-time polymerase chain reaction (qRT-PCR), and their clinical significance was analyzed.

Results: The Kaplan-Meier analysis showed that both overall and cancer-specific survival were significantly longer in patients with low DKK1 expression than in those with high DKK1 expression. The multivariate analysis revealed that overall survival was negatively associated with albumin and positively associated with alkaline phosphatase (ALP), serosal invasion and stage, and cancer-specific survival was positively associated with ALP, portal vein invasion and DKK1 mRNA.

Conclusion: Expression of CSC-associated DKK1 mRNA might be an unfavorable prognostic marker for patients with HCC.

Keywords: CD44; DKK1; cancer stem cells; hepatocellular carcinoma; prognosis.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / pathology
  • Cell Line, Tumor
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Hepatocytes / metabolism
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neoplastic Stem Cells / metabolism*
  • Neoplastic Stem Cells / pathology
  • Prognosis
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Survival Analysis

Substances

  • Biomarkers, Tumor
  • DKK1 protein, human
  • Intercellular Signaling Peptides and Proteins
  • RNA, Messenger