Title:Colorectal Cancer-Associated Fibroblasts are Genotypically Distinct
VOLUME: 10 ISSUE: 2
Author(s):Amy A. Mrazek, Joseph R. Carmical, Thomas G. Wood, Mark R. Hellmich, Mahmoud Eltorky and Celia Chao
Affiliation:Department of Surgery, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555, USA.
Keywords:Carcinoma-associated fibroblasts, colorectal cancer, gene expression, normal colorectal mucosal fibroblasts,
microarray, promoter methylation.
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 iReportTM 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 iReportTM 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.
