Gene expression profiles of primary colorectal carcinomas, liver metastases, and carcinomatoses.
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.


CONCLUSIONS
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 tumorigenesis.
Kleivi
Kristine
K
Department of Genetics, Institute for Cancer Research, Rikshospitalet-Radiumhospitalet Medical Center, Oslo, Norway. ext-kristine.kleivi@vtt.fi
Lind
Guro E
GE
Diep
Chieu B
CB
Meling
Gunn I
GI
Brandal
Lin T
LT
Nesland
Jahn M
JM
Myklebost
Ola
O
Rognum
Torleiv O
TO
Giercksky
Karl-Erik
KE
Skotheim
Rolf I
RI
Lothe
Ragnhild A
RA
D002277:Carcinoma / Q000378:metabolism*; D045744:Cell Line, Tumor; D016000:Cluster Analysis; D003110:Colonic Neoplasms / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000378:metabolism*; D020869:Gene Expression Profiling; D016158:Genes, p53; D020022:Genetic Predisposition to Disease; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000556:secondary; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D010534:Peritoneal Neoplasms / Q000378:metabolism* / Q000556:secondary; D040081:Protein Array Analysis