Seminario CIPF

Seminario CIPF
Prometastatic in tumor-unaffected hepatic tissue from surgical patients with and
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without colorectal cancer
Speaker: Dr. Fernando Vidal
Professor of Human Histology, Cell Biology and Molecular Pathogenesis, Deputy
Director at the Valencia Institute of Pathology - Catholic University of Valencia
Date: 10/06/2016 - 13h
Place: Salón de Actos CIPF
Abstract: Colorectal cancer (CRC) frequently metastasizes to the liver. Hepatic
metastasis development is associated with marked gene expression changes generated
in part at the primary CRC (colorectal cancer), and in part at the secondary site in the
liver, which represents the new microenvironment for metastatic CRC cells.
Additionally, soluble and exosomal proteins released from the primary CRC and other
intraperitoneal organs have remote effects on hepatic gene expression, which trigger a
liver prometastatic reaction in some patients. However, the genetic and phenotypic
properties of specific cancer cells able to implant and grow in the liver have not yet
been established. Neither is it known the contribution of the patient’s genetic,
physiologic and pathologic backgrounds to hepatic CRC metastasis.
We recently studied a set of clinical and experimental hepatic prometastatic genes,
encompassing metabolic bioprotection genes, immune response-related genes,
inflammation-related genes and tissue regeneration-related genes. Liver tissue
samples were obtained under informed consent from 44 patients with CRC without
hepatic metastases, and 23 patients with miscellaneous non-neoplastic
gastrointestinal surgical pathologies. All the biopsies were obtained during the surgical
intervention of recruited patients. TaqMan-low density arrays were used to quantify
hepatic gene expression level.
Despite the low number of included patients, we identified statistically significant
(p<0.01) differences in the expression level of 58% of genes, between patients with
and without CRC. CRC patient-related prometastatic genes included immune responserelated liver genes (66%), inflammation-related liver genes (87%), metabolic
bioprotection liver genes (37%) and liver regeneration genes (16%). Heat map analyses
of patient versus prometastatic gene expression changes demonstrated the segregated
distribution of patients with and without CRC, according to their prometastatic gene
expression patterns. Hierarchical cluster analysis of liver prometastatic genes
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according to their expression level correlation showed two well-differentiated gene
signature having different functional associations in the liver of patients with and
without CRC.
These data demonstrated remarkable changes in the expression level of liver
prometastatic genes between patients with and without CRC, and suggest the
potential interest of identified gene signatures for the individual assessment of hepatic
metastasis risk in CRC patients, and as an in vitro screening method to identify
molecular inhibitors of liver prometastatic genes.