Transcriptional census of 36 microdissected colorectal cancers yields a gene signature to distinguish UICC II and III.
UICC stage II and III colorectal cancers (CRC) differ fundamentally in prognosis and therapeutic concepts. To analyze differential gene expression between both stages and to establish a relationship between molecular background and clinical presentation, tumor material from 36 unselected consecutive patients presenting with sporadic CRC, 18 UICC stage II and 18 UICC stage III, were laser microdissected to separate epithelial tumor cells. Gene expression levels were measured using U133A Affymetrix gene arrays. Twelve CRC associated signal transduction pathways as well as all 22,000 probe sets were screened for differential gene expression. We identified a signature consisting of 45 probe sets that allowed discrimination between UICC stage II and stage III with a rate of correct classification of about 80%. The most distinctive elements in this signature were the gene GSTP-binding elongation factor (GSPT2) and the transcription factor HOXA9. Differential expression of these genes was confirmed by quantitative real-time polymerase chain reaction (p(HOXA9) = 0.04, p(GSTP2) = 0.02). Despite the reliability of the presented data, there was no substantial differential expression of genes in cancer-related pathways. However, the comparison with recently published data corroborates the 45 gene signature showing structural agreement in the direction of fold changes of gene expression levels for our set of genes chosen to discriminate between both stages.
Groene
Joern
J
Department of General, Vascular and Thoracic Surgery, Campus Benjamin Franklin, Charité Universitaetsmedizin, Berlin, Germany. mansmann@ibe.med.uni-muenchen.de
Mansmann
Ulrich
U
Meister
Reinhard
R
Staub
Eike
E
Roepcke
Stefan
S
Heinze
Maya
M
Klaman
Irina
I
Brümmendorf
Thomas
T
Hermann
Klaus
K
Loddenkemper
Christoph
C
Pilarsky
Christian
C
Mann
Benno
B
Adams
Hans-Peter
HP
Buhr
Heinz Johannes
HJ
Rosenthal
André
A
D000368:Aged; D015179:Colorectal Neoplasms / Q000145:classification / Q000235:genetics* / Q000473:pathology*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010454:Peptide Termination Factors / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics*
D018398:Homeodomain Proteins; D010454:Peptide Termination Factors; D012333:RNA, Messenger; C097899:homeobox protein HOXA9; C087971:peptide-chain-release factor 3