Background Despite the fact that metastases are the leading cause of
colorectal cancer deaths, little is known about the underlying molecular
changes in these advanced disease stages. Few have studied the overall gene
expression levels in metastases from colorectal carcinomas, and so far, none
has investigated the peritoneal carcinomatoses by use of DNA microarrays.
Therefore, the aim of the present study is to investigate and compare the gene
expression patterns of primary carcinomas (n = 18), liver metastases (n = 4),
and carcinomatoses (n = 4), relative to normal samples from the large bowel.
Results Transcriptome profiles of colorectal cancer metastases independent
of tumor site, as well as separate profiles associated with primary
carcinomas, liver metastases, or peritoneal carcinomatoses, were assessed by
use of Bayesian statistics. Gains of chromosome arm 5p are common in
peritoneal carcinomatoses and several candidate genes (including PTGER4, SKP2,
and ZNF622) mapping to this region were overexpressed in the tumors.
Expression signatures stratified on TP53 mutation status were identified
across all tumors regardless of stage. Furthermore, the gene expression levels
for the in vivo tumors were compared with an in vitro model consisting of
cell lines representing all three tumor stages established from one patient.
Conclusion By statistical analysis of gene expression data from primary
colorectal carcinomas, liver metastases, and carcinomatoses, we are able to
identify genetic patterns associated with the different stages of