Differential Network Analysis Applied to Preoperative Breast Cancer Chemotherapy Response

摘要: In silico approaches are increasingly considered to improve breast cancer treatment. One of these treatments, neoadjuvant TFAC chemotherapy, is used in cases where application preoperative systemic therapy indicated. Estimating response treatment allows or improves clinical decision-making and this, turn, may be based on a good understanding the underlying molecular mechanisms. Ever increasing amounts high throughput data become available for integration into functional networks. this study, we applied our software tool ExprEssence identify specific mechanisms relevant response, from gene/protein interaction network. We contrasted resulting active subnetwork subnetworks two other such methods, OptDis KeyPathwayMiner. could show that more related mechanistic principles than methods despite simplicity ExprEssence. were able validate method by recovering known as an example method, identified mechanism further explain synergism between paclitaxel doxorubicin treatment: Paclitaxel attenuate MELK gene expression, lower levels its target MYBL2, already associated with hepatocellular carcinoma cell lines. tested hypothesis three lines, confirming it part. particular, predicted effect MYBL2 validated, synergistic demonstrated lines SKBR3 MCF-7.