Figure 5.

The shortest pathway identified by our system. Pathways including the gene CEBPD and SOD1 were the shortest pathways in our computational results, which indicates SOD1 (p-value = 4.01E-04) does not interact with other genes or pathways. We were curious about what caused the chemoresistant mechanism after SOD1 was regulated. Cisplatin caused DNA damage as well as reactive oxygen species (ROS), which triggered cell cycle arrest or/and apoptosis. Cisplatin induced CEBPD by an as of yet unidentified mechanism which activated the SOD1 gene expression. Superoxide anion (O2•-) is dismutated by SOD1 and converted to H2O2 which can be further neutralized to water and oxygen by catalase [23]. The reduced ROS levels in their model caused the cisplatin-resistant phenotype. These results call for an assessment of CEBPD and SOD1 expression in bladder tumors as a potential means of predicting cisplatin resistance. According to our computational results, SOD1 has significant differential expressions between chemosensitive and chemoresistant array data and is activated by CEBPD as well. We may make a reasonable assumption that this phenomenon occurs in ovarian chemoresistance. Based on this biological evidence and our computational experiment results, we can infer that SOD1 plays a critical role in ovarian chemoresistance.

Chao et al. BMC Medical Genomics 2011 4:23   doi:10.1186/1755-8794-4-23
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