Clinical significance and expression of cyclin kinase subunits 1 and 2 in hepatocellular carcinoma

Liver Int. 2010 Jan;30(1):119-25. doi: 10.1111/j.1478-3231.2009.02106.x. Epub 2009 Oct 21.

Abstract

Background: The mammalian cyclin kinase subunit (Cks) family has two members, Cks1 and Cks2, which were identified based on the protein sequence homology to yeast Cks. Overexpression of Cks1 and Cks2 has been reported to be associated with high aggressiveness and a poor prognosis in various malignancies, including gastric, breast and prostate carcinomas. Yet, whether Cks1 and Cks2 are overexpressed in hepatocellular carcinoma (HCC) remains uncharacterized.

Aims: To investigate whether overexpression of the Cks family is clinically relevant to HCC, and whether expression patterns of Cks1 and Cks2 in HCC have diagnostic and prognostic value.

Methods: Real-time quantitative reverse transcriptase polymerase chain reaction, immunostaining and Western blot analyses were used to detect the expression of Cks1 and Cks2 at the mRNA and protein levels respectively. The associations between Cks1 and Cks2 expressions and clinical features, as well as the association between Cks1 or Cks2 and p27(kip1) expressions in HCC, were analysed.

Results: Expressions of Cks1 and Cks2 at both mRNA and protein levels were significantly higher in HCC than those in the adjacent noncancerous tissues (including chronic hepatitis and cirrhosis) and normal liver tissues. Overexpressions of Cks1 and Cks2 in HCC were closely associated with poor differentiation features. The expressions of both Cks1 and Cks2 were negatively associated with p27(kip1) at the protein level.

Conclusions: Overexpression of Cks1 and Cks2 is associated with the aggressive tumour behaviours of HCC, and thus has diagnostic and prognostic value. Further efforts are needed to develop novel biomarkers for HCC based on CKs1 and Cks2 expressions.

MeSH terms

  • Biomarkers, Tumor / metabolism
  • CDC2-CDC28 Kinases
  • Carcinoma, Hepatocellular / diagnosis
  • Carcinoma, Hepatocellular / enzymology*
  • Carcinoma, Hepatocellular / genetics
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Count
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cyclin I / genetics
  • Cyclin I / metabolism*
  • Cyclin-Dependent Kinase Inhibitor p27 / genetics
  • Cyclin-Dependent Kinase Inhibitor p27 / metabolism
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Neoplastic
  • Hepatitis, Chronic / diagnosis
  • Hepatitis, Chronic / enzymology
  • Hepatitis, Chronic / genetics
  • Humans
  • Liver Cirrhosis / diagnosis
  • Liver Cirrhosis / enzymology
  • Liver Cirrhosis / genetics
  • Liver Neoplasms / diagnosis
  • Liver Neoplasms / enzymology*
  • Liver Neoplasms / genetics
  • Prognosis
  • Protein Kinases / genetics
  • Protein Kinases / metabolism*
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Biomarkers, Tumor
  • CCNI protein, human
  • Carrier Proteins
  • Cell Cycle Proteins
  • Cyclin I
  • RNA, Messenger
  • Cyclin-Dependent Kinase Inhibitor p27
  • Protein Kinases
  • CDC2-CDC28 Kinases
  • CKS2 protein, human