SUPERTAM_HGU133A Gene Set Enrichment Analysis (GSEA) in term of lymph node and distant metastasis

Background Lymph node status is generally considered as one of the best prognostic factors in breast cancer. However, association between nodal and distant metastasis is not straightforward. Here we analyze differences between molecular mechanisms responsible for nodal and distant metastasis, and the impact of molecular subtype on this association. Methods We use SUPERTAM_HGU133A cohort of 836 patients with full microarray data available. Logistic regression evaluates distant metastasis risk, and Gene Set Enrichment Analysis (GSEA) is used to identify molecular mechanisms targetable in the key clinical scenarios. Results GSEA shows different molecular background for lymph node and distant metastasis and unique patterns of deregulated molecular processes in tumors of four breast cancer subtypes. Risk of distant metastasis in node positive luminal A patients is strong in SUPERTAM_HGU133A (OR: 2.401, CI: 1.316-4.380) dataset. For luminal A tumors, nodal positivity is associated with enrichment of NF-κB and Src, while distant metastasis is associated with strong mechanisms of cell cycle regulation, thrombolysis, DNA-repair, and immune response. Based on GSEA results, we select panels of promising inhibitors applicable for the key clinical scenarios depending on lymph node status that are currently being tested in vitro, in vivo, or in clinical trials. Conclusions Potential molecular targets are different for nodal and distant metastasis in breast cancer and are highly variable among different molecular subtypes. Panels of inhibitors have potential to improve the outcome of luminal A breast cancer patients based on lymph node status. We hope that further clinical trials have potential to translate the current knowledge from the laboratory to an improved treatment of breast cancer patients.