INVESTIGADORES
FERNANDEZ elmer Andres
congresos y reuniones científicas
Título:
Gender-specific tumor pathways in colon cancer revealed by ontology analysis of tissue by gender gene interaction patterns.
Autor/es:
FERNÁNDEZ, ELMER ANDRÉS; SALVATIERRA, EDGARDO; GIDEKEL, MANUEL; FRESNO, CRISTOBAL; BALZARINI, MÓNICA; PODHAJCER, OSVALDO LUIS
Lugar:
cordoba
Reunión:
Congreso; 2do Congreso Argentino de Bioinformatica y Biologia Computacional; 2011
Institución organizadora:
Asociacion Argentina de Bioinformatica y Biologia Computacional
Resumen:
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It is well
know that diseases develop differently in male and female subjects,
however most of the gene expression experiments carried on in last
years do not tackle this issue. Here we show that Gender specific
pathways emerge when analyzing gene expression interaction patters.
Twenty two
microarrays to explore colon cancer from twenty two subjects (Table
1) where used (GEO data set GSE4107) for the analysis. A gene by gene
linear model accounting for Treatment by Gender interaction effect
where applied and 440 differentially expressed genes (DEG) were
identified. This DEG list was analyzed through DAVID ontology tool[1]
to look for enriched Gene Ontology (GO) terms. DAVID results where
integrated with expression information and the ontology tree was
displayed. Enriched terms (ET) were color-coded according to the
ratio between up and down regulated genes belonging to the GO term.
The integration tool allows us to identify fully Up/Down expressed
ETs. Two GO tree branches related to immune response sharing many
genes were recognized (Figure 1) holding only genes with negative
interaction effect. From this ETs, five DEG (GIMAP5, SASH3, OSMR and
STAT5A) related to response to stimulus specifically to the positive
regulation of T-cell differentiation were found. They where over
expressed in Male Tumors but not in Female nor in normal tissue. By
means of Genemania web tool [2] we could see a net that involve
STAT5A and OSMR thought JAK1 suggesting a differential level of
activation of that pathway in male tumor. This pathway has been
linked to tumor progression by stimulating cell proliferation and
preventing apoptosis. Activation of STAT5, which is dependent on
Bcr/Abl kinase activity, has been shown primarily in leukemia.
Phospho-STAT5 has been linked to the aggressiveness of solid tumors,
such as prostate cancer, breast cancer, hepatocellular carcinoma and
CRC cell growth, cell cycle progression, invasion and migration
through the regulation of target gene expression[3].