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.