Microsatellite instability status affects gene expression profiles in early onset colorectal cancer patients

J Surg Res. 2013 Dec;185(2):626-37. doi: 10.1016/j.jss.2013.07.014. Epub 2013 Jul 31.

Abstract

Background: The association between microsatellite instability (MSI) status and gene expression profiles in the early onset sporadic colorectal cancer (CRC) has not been clearly established. The aim of this study was to identify the altered gene expression patterns depending on the MSI status of early onset CRC and determine specific biomarkers that could provide novel therapeutic molecular targets in the Turkish population.

Materials and methods: MSI markers (BAT25, BAT26, D2S123, D5S346, and D17S250) were investigated in tumors from 36 early onset sporadic CRC patients in whom gene expression profiles were analyzed previously. The relationship between the gene expression profiles depending on MSI status was evaluated.

Results: A total of 15 tumors (16.66%) were identified as having MSI and 21 tumors (58.33%) were identified as having microsatellite stability (MSS). CK20 and MAP3K8 upregulation, observed in MSS tumors, was significantly associated with lymph node metastasis, recurrence, and/or distant metastasis and a short median survival (P < 0.05). REG1A upregulation is also correlated with recurrence and/or distant metastasis and a short median survival in patients with MSI tumors (P < 0.05).

Conclusions: High expression levels of CK20 and MAP3K8 in MSS tumors and REG1A in MSI tumors correlated with a poor prognosis in CRC patients. Further studies and validations are required; these genes may provide novel therapeutic molecular targets for the development of anticancer drugs related to MSI status for early onset CRC treatment.

Keywords: CK20; Colorectal cancer; Early onset; MAP3K8; MSI; MSS; REG1A.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age of Onset
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / secondary
  • DNA Methylation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Genetic Markers*
  • Genetic Testing
  • Humans
  • Keratin-20 / genetics
  • Lithostathine / genetics
  • Lymphatic Metastasis / genetics
  • MAP Kinase Kinase Kinases / genetics
  • Male
  • Microsatellite Instability*
  • Middle Aged
  • Prognosis
  • Proto-Oncogene Proteins / genetics
  • Transcriptome*
  • Young Adult

Substances

  • Genetic Markers
  • Keratin-20
  • Lithostathine
  • Proto-Oncogene Proteins
  • REG1A protein, human
  • MAP Kinase Kinase Kinases
  • MAP3K8 protein, human