A multimarker qPCR platform for the characterisation of endometrial cancer

Oncol Rep. 2014 Feb;31(2):1003-13. doi: 10.3892/or.2013.2924. Epub 2013 Dec 13.

Abstract

The molecular background of endometrial cancer (EC) has not been fully elucidated. In the present study, we developed a quantitative PCR (qPCR) platform to examine the gene dosages of the potential molecular markers MGB1, TOP2A, ERBB1-4, MYC, CCND1, ESR1 and PI3K. The platform was applied in samples collected from 157 EC patients (stage I-IV) to verify its clinical utility and to examine the diagnostic and prognostic significance of the analysed biomarkers. The gene dosage pattern of the ERBB family and its downstream effectors PI3K and MYC showed particularly strong correlations with clinicopathological data. The ERBB PI3K/Akt pathway was upregulated in 31 (20%) of 156 cases. Activation of the ERBB PI3K/Akt pathway was positively correlated with a higher stage (p=0.001), higher grade (p=0.001), histological type II disease (p=0.0003) and metastases (p=0.02). The implemented hierarchical clustering revealed that cluster 2 was characterised by high copy numbers of the studied genes. Cluster 2 was associated with shorter overall survival (p=0.05). The platform was found to be a fast and simple method for direct analysis of the genes involved in uterine carcinogenesis, making it feasible for EC biology characterisation.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, Neoplasm / genetics
  • Biomarkers, Tumor / genetics*
  • Cyclin D1 / genetics
  • DNA Topoisomerases, Type II / genetics
  • DNA-Binding Proteins / genetics
  • Endometrial Neoplasms / genetics*
  • ErbB Receptors / genetics
  • Estrogen Receptor alpha / genetics
  • Female
  • Gene Dosage / genetics*
  • Humans
  • Mammaglobin A / genetics
  • Middle Aged
  • Phosphatidylinositol 3-Kinases / genetics
  • Poly-ADP-Ribose Binding Proteins
  • Polymerase Chain Reaction
  • Proto-Oncogene Proteins c-myc / genetics
  • RNA, Messenger / biosynthesis

Substances

  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • CCND1 protein, human
  • DNA-Binding Proteins
  • ESR1 protein, human
  • Estrogen Receptor alpha
  • MYC protein, human
  • Mammaglobin A
  • Poly-ADP-Ribose Binding Proteins
  • Proto-Oncogene Proteins c-myc
  • RNA, Messenger
  • SCGB2A2 protein, human
  • Cyclin D1
  • ErbB Receptors
  • DNA Topoisomerases, Type II
  • TOP2A protein, human