Gender-specific tumor pathways in colon cancer revealed by ontology analysis of tissue by gender gene interaction patterns.

FERNÁNDEZ, ELMER ANDRÉS; SALVATIERRA, EDGARDO; GIDEKEL, MANUEL; FRESNO, CRISTOBAL; BALZARINI, MÓNICA; PODHAJCER, OSVALDO LUIS

cordoba

Congreso; 2do Congreso Argentino de Bioinformatica y Biologia Computacional; 2011

Asociacion Argentina de Bioinformatica y Biologia Computacional

<!-- @page { margin: 0.79in } P { margin-bottom: 0.08in } --> 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].