Comprehensive analysis of the clinical significance of inducing pluripotent stemness-related gene expression in colorectal cancer cells

Ann Surg Oncol. 2009 Sep;16(9):2638-44. doi: 10.1245/s10434-009-0567-5. Epub 2009 Jun 25.

Abstract

Background: We previously determined that cancer stem-like cells may influence the susceptibility of colorectal cancer (CRC) cells to chemotherapeutic agents. Although Takahashi and Park identified a set of induced pluripotent stem cell (iPS)-related genes required for normal stem cell maintenance, the precise role of iPS-related gene expression in CRC pathogenesis remains to be determined. The purpose of this study was to clarify the clinical relevance of "stemness"-regulating gene expression in CRC cases.

Materials and methods: Cancer cells were excised from tissues of 79 CRC cases by laser microdissection (LMD), and quantitative RT-PCR was used to evaluate expression levels of the iPS-related genes c-MYC, SOX2, OCT3/4, LIN28, KLF4, and NANOG, and to identify any associations between their expression and clinicopathological CRC progression.

Results: We found that LIN28 expression is significantly associated with lymph node metastasis (p = 0.018) and Dukes stage (p = 0.0319). SOX2expression is also correlated with lymph node metastasis. Furthermore, the ten cases with Dukes D disease expressed significantly higher levels of SOX2transcript than the other 69 cases (p = 0.0136). In contrast, KLF4 expression was inversely related to Dukes stage. Expression of c-MYC, OCT3/4, and NANOG did not appear to have clinical relevance in CRC cases.

Conclusion: The present analysis strongly suggests that altered expression of several iPS-related genes plays a role in CRC pathogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / metabolism
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology*
  • Gene Expression Regulation, Neoplastic
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Humans
  • Kruppel-Like Factor 4
  • Kruppel-Like Transcription Factors / genetics
  • Kruppel-Like Transcription Factors / metabolism
  • Lasers
  • Lymphatic Metastasis
  • Microdissection
  • Nanog Homeobox Protein
  • Neoplasm Staging
  • Octamer Transcription Factor-3 / genetics
  • Octamer Transcription Factor-3 / metabolism
  • Pluripotent Stem Cells / metabolism*
  • Pluripotent Stem Cells / pathology*
  • Prognosis
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • SOXB1 Transcription Factors / genetics
  • SOXB1 Transcription Factors / metabolism

Substances

  • Biomarkers, Tumor
  • Homeodomain Proteins
  • KLF4 protein, human
  • Kruppel-Like Factor 4
  • Kruppel-Like Transcription Factors
  • Lin28A protein, human
  • MYC protein, human
  • NANOG protein, human
  • Nanog Homeobox Protein
  • Octamer Transcription Factor-3
  • POU5F1 protein, human
  • Proto-Oncogene Proteins c-myc
  • RNA, Messenger
  • RNA-Binding Proteins
  • SOX2 protein, human
  • SOXB1 Transcription Factors