Molecular signature for lymphatic metastasis in colorectal carcinomas.
OBJECTIVE
TNM-staging of colorectal carcinomas (CRC) relies on the histopathologic workup of the surgically removed specimen. If valid preoperative staging methods existed, patients could be selected for adequate individual therapy before surgery. Microarray techniques provide a promising tool to identify stage-specific molecular signatures on primary tumor biopsies.


METHODS
Forty tumor samples of stage UICC I, II CRC, 40 samples of stage III CRC, and 25 biopsies of healthy mucosa (MC) were shock frozen in liquid nitrogen and underwent cryotomy after manual dissection for tumor tissue or MC enrichment. Isolated RNA was hybridized to GeneChips (HG-U133A, Affymetrix). Preprocessing of the microarray results was done by the robust multichip average method, and differentially expressed genes were selected by the maximum Wilcoxon statistic over 22,215 probe sets. The results were validated at an independent clinical study.


RESULTS
Fifty differently expressed genes between stage UICC I, II versus III CRC were identified respecting the selection criteria by allowing for multiple testing. The data validation by the independent clinical study confirmed our results. In comparison to MC, the genes were over- or underexpressed. They belong to various functional groups such as cellular adhesion, transporters, signaling, metabolism, protein synthesis, gene control, and immune system.


CONCLUSIONS
Our large patient cohort and the data validation on an independent study identified 50 differentially expressed genes between CRC of different histopathologic stages. These findings indicate that molecular staging of CRC may be possible, which could help to guide individual CRC treatment before surgery.
Croner
Roland S
RS
Department of Surgery, University of Erlangen-Nuremberg, Erlangen, Germany. Roland.Croner@uk-erlangen.de
Förtsch
Thomas
T
Brückl
Wolfgang M
WM
Rödel
Franz
F
Rödel
Claus
C
Papadopoulos
Thomas
T
Brabletz
Thomas
T
Kirchner
Thomas
T
Sachs
Martin
M
Behrens
Jürgen
J
Klein-Hitpass
Ludger
L
Stürzl
Michael
M
Hohenberger
Werner
W
Lausen
Berthold
B
D000368:Aged; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology*; D016022:Case-Control Studies; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology*; D005260:Female; D015870:Gene Expression / Q000502:physiology*; D020869:Gene Expression Profiling; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D015203:Reproducibility of Results