Cancers, Vol. 12, Pages 2638: How Different Are the Molecular Mechanisms of Nodal and Distant Metastasis in Luminal A Breast Cancer?

Cancers, Vol. 12, Pages 2638: How Different Are the Molecular Mechanisms of Nodal and Distant Metastasis in Luminal A Breast Cancer? Cancers doi: 10.3390/cancers12092638 Authors: Petr Lapcik Anna Pospisilova Lucia Janacova Peter Grell Pavel Fabian Pavel Bouchal Lymph node status is one of the best prognostic factors in breast cancer, however, its association with distant metastasis is not straightforward. Here we compare molecular mechanisms of nodal and distant metastasis in molecular subtypes of breast cancer, with major focus on luminal A patients. We analyze a new cohort of 706 patients (MMCI_706) as well as an independent cohort of 836 primary tumors with full gene expression information (SUPERTAM_HGU133A). We evaluate the risk of distant metastasis, analyze targetable molecular mechanisms in Gene Set Enrichment Analysis and identify relevant inhibitors. Lymph node positivity is generally associated with NF-κB and Src pathways and is related to high risk (OR: 5.062 and 2.401 in MMCI_706 and SUPERTAM_HGU133A, respectively, p < 0.05) of distant metastasis in luminal A patients. However, a part (≤15%) of lymph node negative tumors at the diagnosis develop the distant metastasis which is related to cell proliferation control and thrombolysis. Distant metastasis of lymph node positive patients is mostly associated with immune response. These pro-metastatic mechanisms further vary in other molecular subtypes. Our data indic...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research