Weighted gene co-expression network analysis in identification of endometrial cancer prognosis markers

Asian Pac J Cancer Prev. 2012;13(9):4607-11. doi: 10.7314/apjcp.2012.13.9.4607.

Abstract

Objective: Endometrial cancer (EC) is the most common gynecologic malignancy. Identification of potential biomarkers of EC would be helpful for the detection and monitoring of malignancy, improving clinical outcomes.

Methods: The Weighted Gene Co-expression Network Analysis method was used to identify prognostic markers for EC in this study. Moreover, underlying molecular mechanisms were characterized by KEGG pathway enrichment and transcriptional regulation analyses.

Results: Seven gene co-expression modules were obtained, but only the turquoise module was positively related with EC stage. Among the genes in the turquoise module, COL5A2 (collagen, type V, alpha 2) could be regulated by PBX (pre-B-cell leukemia homeobox 1)1/2 and HOXB1(homeobox B1) transcription factors to be involved in the focal adhesion pathway; CENP-E (centromere protein E, 312kDa) by E2F4 (E2F transcription factor 4, p107/p130-binding); MYCN (v-myc myelocytomatosis viral related oncogene, neuroblastoma derived [avian]) by PAX5 (paired box 5); and BCL-2 (B-cell CLL/ lymphoma 2) and IGFBP-6 (insulin-like growth factor binding protein 6) by GLI1. They were predicted to be associated with EC progression via Hedgehog signaling and other cancer related-pathways.

Conclusions: These data on transcriptional regulation may provide a better understanding of molecular mechanisms and clues to potential therapeutic targets in the treatment of EC.

MeSH terms

  • Analysis of Variance
  • Biomarkers, Tumor / genetics*
  • Chromosomal Proteins, Non-Histone / genetics
  • Collagen Type V / genetics
  • DNA-Binding Proteins / genetics
  • E2F4 Transcription Factor / genetics
  • Endometrial Neoplasms / genetics*
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Homeodomain Proteins / genetics
  • Humans
  • Insulin-Like Growth Factor Binding Protein 6 / genetics
  • N-Myc Proto-Oncogene Protein
  • Nuclear Proteins / genetics
  • Oncogene Proteins / genetics
  • PAX5 Transcription Factor / genetics
  • Pre-B-Cell Leukemia Transcription Factor 1
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Signal Transduction / genetics
  • Transcription Factors / genetics
  • Transcription, Genetic
  • Zinc Finger Protein GLI1

Substances

  • Biomarkers, Tumor
  • Chromosomal Proteins, Non-Histone
  • Collagen Type V
  • DNA-Binding Proteins
  • E2F4 Transcription Factor
  • E2F4 protein, human
  • GLI1 protein, human
  • HOXB1 homeodomain protein
  • Homeodomain Proteins
  • Insulin-Like Growth Factor Binding Protein 6
  • MYCN protein, human
  • N-Myc Proto-Oncogene Protein
  • Nuclear Proteins
  • Oncogene Proteins
  • PAX5 Transcription Factor
  • PAX5 protein, human
  • Pre-B-Cell Leukemia Transcription Factor 1
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Transcription Factors
  • Zinc Finger Protein GLI1
  • centromere protein E
  • PBX1 protein, human