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.
Keywords: Carcinoma-associated fibroblasts, colorectal cancer, gene expression, normal colorectal mucosal fibroblasts, microarray, promoter methylation.
Current Cancer Therapy Reviews
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:
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.
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Mrazek A. Amy, Carmical R. Joseph, Wood G. Thomas, Hellmich R. Mark, Eltorky Mahmoud and Chao Celia, Colorectal Cancer-Associated Fibroblasts are Genotypically Distinct, Current Cancer Therapy Reviews 2014; 10 (2) . https://dx.doi.org/10.2174/157339471002141124123103
DOI https://dx.doi.org/10.2174/157339471002141124123103 |
Print ISSN 1573-3947 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6301 |
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