Expression and prognostic significance of kallikrein-related peptidase 8 protein levels in advanced ovarian cancer by using automated quantitative analysis

Thromb Haemost. 2009 Mar;101(3):541-6.

Abstract

Kallikrein-related peptidases, a subgroup of the serine protease enzyme family, are considered to be important prognostic biomarkers in cancer. In this study we sought to determine the prognostic value of kallikrein-related peptidase 8 (KLK8, hK8, KLK-8) in ovarian cancer using a novel method of compartmentalised in situ protein analysis. A tissue array composed of 150 advanced stage ovarian cancers, uniformly treated with surgical debulking followed by platinum-paclitaxel combination chemotherapy, was constructed. For the evaluation of kallikrein-related peptidase 8 protein expression, we used an immunofluorescence-based method of automated in situ quantitative protein analysis (AQUA). Mean follow-up time of the cohort was 34.35 months. One hundred twenty-six of 150 cases had sufficient tissue for AQUA analysis. There were significant correlations between tumour mask KLK8 protein expression levels and clinicopathological variables, including grade (p = 0.0011), residual disease (p = 0.0063) and clinical response to chemotherapy(p = 0.0346). In univariate survival analysis there was a significant correlation between KLK8 tumour mask expression and five years progression-free survival, meanwhile it was not associated with five-year overall survival (p = 0.0694). Specifically, low KLK8 expression correlated with better outcome (top vs. bottom quartile, p = 0.0319). In multivariate survival analysis, adjusting for well-characterised prognostic variables, tumour KLK8 expression level retained its prognostic significance for progression-free survival (95%CI: 0.341-1.027, p = 0.045). The possibility that KLK8 may be a suitable candidate as a diagnostic and prognostic marker warrants further investigation.

Publication types

  • Evaluation Study

MeSH terms

  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / genetics
  • Disease-Free Survival
  • Female
  • Humans
  • Immunohistochemistry
  • Kallikreins / analysis*
  • Kallikreins / genetics*
  • Ovarian Neoplasms / diagnosis*
  • Ovarian Neoplasms / pathology
  • Prognosis
  • Protein Array Analysis / methods*
  • Tissue Array Analysis / methods*

Substances

  • Biomarkers, Tumor
  • KLK8 protein, human
  • Kallikreins