Metastatic transcriptional pattern revealed by gene expression profiling in primary colorectal carcinoma.
Metastatic spread to the liver is the major contributor to mortality in patients with colorectal carcinoma (CRC). In order to seek for gene expression patterns associated with metastatic potential in primary CRC, we compared the transcriptional profiles of 10 radically resected primary CRCs from patients who did not develop distant metastases within a 5-year follow-up period with those of 10 primary/metastatic tumor pairs from patients with synchronous liver metastases. To focus selectively on neoplastic cells, the study was conducted on laser-microdissected bioptic tissues. Arrays of 7,864 human cDNAs were utilized. While a striking transcriptional similarity was observed between the primary tumors and their distant metastases, the nonmetastasizing primary tumors were clearly distinct from the primary/metastatic tumor pairs. Of 37 gene expression differences found between the 2 groups of primary tumors, 29 also distinguished nonmetastasizing tumors from metastases. The gene encoding for mannosyl (alpha-1,3-)-glycoprotein beta-1,4-N-acetyl-glucosaminyl-transferase (GnT-IV) became significantly upregulated in primary/metastatic tumor pairs (p < 0.001). GnT-IV upregulation was confirmed by RT-PCR. These data support the existence of a specific transcriptional signature distinguishing primary colon adenocarcinomas with different metastatic potential, the further pursuit of which may lead to relevant clinical and therapeutic applications.
D'Arrigo
Antonello
A
Research and Innovation Company, Padova, Italy. darrigo@researchinnovation.com
Belluco
Claudio
C
Ambrosi
Alessandro
A
Digito
Maura
M
Esposito
Giovanni
G
Bertola
Antonella
A
Fabris
Michele
M
Nofrate
Valentina
V
Mammano
Enzo
E
Leon
Alberta
A
Nitti
Donato
D
Lise
Mario
M
D000230:Adenocarcinoma / Q000235:genetics* / Q000556:secondary; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007834:Lasers; D008175:Lung Neoplasms / Q000235:genetics* / Q000556:secondary; D008297:Male; D008875:Middle Aged; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics*; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic
D014408:Biomarkers, Tumor; D017351:N-Acetylglucosaminyltransferases; C038111:alpha-1,3-mannosylglycoprotein beta-1,4-N-acetylglucosaminyltransferase