Overexpression of CK20, MAP3K8 and EIF5A correlates with poor prognosis in early-onset colorectal cancer patients

J Cancer Res Clin Oncol. 2013 Apr;139(4):691-702. doi: 10.1007/s00432-013-1372-x. Epub 2013 Jan 16.

Abstract

Purpose: Due to ethnic, genetic and environmental factors, the clinical and molecular characteristics of Turkish colorectal cancer (CRC) patients are different from those of Western populations. The aim of this study was to clarify the relevant alterations of gene expression associated with colorectal carcinogenesis in early-onset patients and to identify specific biomarkers that could provide novel therapeutic molecular targets in this population.

Methods: The expression profiles of 114 different genes were evaluated using mRNA PCR arrays in 39 tumors and 20 surgical margin tissue samples from 39 sporadic CRC patients diagnosed at less than 50 years of age.

Results: The expression levels of IMPDH2, CK20, MAP3K8 and EIF5A were strongly up-regulated in CRC tissues compared with normal colorectal tissues (p < 0.05). The highly significant expression ratios of CK20, MAP3K8 and EIF5A observed in the colorectal tumors of patients predicted recurrence (p < 0.05). The expression of IMPDH2, CK20, MAP3K8 and EIF5A was significantly higher in the tumors of patients with short median survival (log-rank p value < 0.05). Progression-free survival was also significantly increased in patients with low expression of the EIF5A gene compared with those who exhibited high expression of this gene (log-rank p value < 0.05).

Conclusion: We demonstrated that high CK20, MAP3K8 and EIF5A expression levels were significant prognostic factors for poor overall survival in CRC patients. Further studies and validations are required; these genes may provide novel therapeutic molecular targets for CRC treatment, as well as new directions for the development of anticancer drugs.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Case-Control Studies
  • Colon / metabolism
  • Colon / pathology
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / mortality*
  • Female
  • Follow-Up Studies
  • Gene Expression Profiling
  • Humans
  • Immunoenzyme Techniques
  • Keratin-20 / genetics
  • Keratin-20 / metabolism*
  • MAP Kinase Kinase Kinases / genetics
  • MAP Kinase Kinase Kinases / metabolism*
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / metabolism
  • Neoplasm Recurrence, Local / mortality*
  • Neoplasm Staging
  • Oligonucleotide Array Sequence Analysis
  • Peptide Initiation Factors / genetics
  • Peptide Initiation Factors / metabolism*
  • Prognosis
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • RNA, Messenger / genetics
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Real-Time Polymerase Chain Reaction
  • Rectum / metabolism
  • Rectum / pathology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Survival Rate
  • Young Adult

Substances

  • Biomarkers, Tumor
  • Keratin-20
  • Peptide Initiation Factors
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • RNA-Binding Proteins
  • eukaryotic translation initiation factor 5A
  • MAP Kinase Kinase Kinases
  • MAP3K8 protein, human