Colorectal cancer-associated fibroblasts are genotypically distinct

Amy A. Mrazek, Joseph R. Carmical, Thomas G. Wood, Mark R. Hellmich, Mahmoud Eltorky, Celia Chao

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Cells in the stromal microenvironment facilitate colorectal cancer (CRC) progression and “co-evolve” with the epithelial cancer cells. Genetic and epigenetic differences between normal colorectal mucosa fibroblasts (NF) and carcinoma- associated fibroblasts (CAF) are not known. The aim of this study is to identify differentially expressed genes and promoter methylation between NF and CAF in human CRC. RNA and DNA were extracted from cultured NF and CAF from CRC resections. Genome-wide gene expression and methylation analyses were performed using the Illumina Human HT-12 v4.0 Expression and Illumina Human Methylation27 BeadChips. Gene expression values between NF and CAF were compared and correlated with methylation patterns. Data was analyzed with Partek Genomics Suite using one-way ANOVA and p<0.05 as significant. Ingenuity iReport™ was performed to identify potential differences in biological functions and pathways between the NF and CAF. Paired methylation and gene expression analyses from 11 NF and 10 CAF colorectal samples are reported. Unsupervised analysis of differentially expressed genes using iReport™ identified “Top Diseases” as “Cancer” and “Colorectal Cancer”. Previous genome wide studies have focused on the cancer cells. We have identified differentially expressed genes and differentially methylated promoter regions that are CAF-specific in CRC.

Original languageEnglish (US)
Pages (from-to)97-218
Number of pages122
JournalCurrent Cancer Therapy Reviews
Volume10
Issue number3
StatePublished - Jan 1 2014

Keywords

  • Carcinoma-associated fibroblasts
  • Colorectal cancer
  • Gene expression
  • Microarray
  • Normal colorectal mucosal fibroblasts
  • Promoter methylation

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Cancer Research

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  • Cite this

    Mrazek, A. A., Carmical, J. R., Wood, T. G., Hellmich, M. R., Eltorky, M., & Chao, C. (2014). Colorectal cancer-associated fibroblasts are genotypically distinct. Current Cancer Therapy Reviews, 10(3), 97-218.