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Gene-expression profile of colorectal adenocarcinoma tissues identified by gene microarray analysis.

3651 Background: Several genes are differentially expressed during the multistep process of colorectal carcinogenesis. The human U133A array (Affymetrix) provides a representation of 22.000 genes. Aim of the study was to identify the gene expression of colorectal adenocarcinoma tissues compared to the normal mucosa.


METHODS
RNA was extracted from 3 samples of moderately differentiated sporadic rectal adenocarcinoma and 3 samples of normal rectal mucosa obtained from the same patients and hybridized against the human U133A array set. Gene expression of tumoral tissues and normal samples was compared; a minimum of 3 times fold differential expression among the same genes in neoplastic and normal samples was considered as significant. Real-time PCR (Roche, Manheim) using the same RNA was also performed on a pool of either up- or down-regulated randomly-selected genes to validate the results.


RESULTS
Approximately 550 genes showed a significant differential expression in adenocarcinomas compared to normal mucosa. 537 genes were upregulated while 13 genes were downregulated in neoplastic tissues. The up-regulated genes included angiogenic factors (VEGF, PD-ECGF, EGF), markers of proliferation (PCNA), tumoral markers (CEA, ACE), genes involved in chemotherapy activity (Farnesyl-transferase, Topoisomerase-1) and several other genes of unclear function. The down-regulated genes included transcription factors (SPIB), adhesion molecules (Desmin), anti-oxidant (GPX3) and other genes of unclear activity. RT-PCR confirmed the results obtained by the microarray analysis.


CONCLUSIONS
Colorectal cancer tissues show a different gene expression compared to the normal mucosa. This differential expression includes several known genes involved in cell growth, angiogenesis, transcription and proliferation as well as other genes of unclear activity, which have never previously been associated with cancer. The identification of a panel of genes specifically expressed in neoplastic tisssues may provide a new tool for the molecular diagnosis of colorectal cancer and furnish new molecular targets for innovative therapeutical strategies. No significant financial relationships to disclose.