How Different Are the Molecular Mechanisms of Nodal and Distant Metastasis in Luminal A Breast Cancer?

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Publikace nespadá pod Lékařskou fakultu, ale pod Přírodovědeckou fakultu. Oficiální stránka publikace je na webu muni.cz.

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LAPČÍK Petr POSPÍŠILOVÁ Anna JANÁČOVÁ Lucia GRELL Peter FABIAN Pavel BOUCHAL Pavel

Rok publikování 2020
Druh Článek v odborném periodiku
Časopis / Zdroj Cancers
Fakulta / Pracoviště MU

Přírodovědecká fakulta

Citace
www https://doi.org/10.3390/cancers12092638
Doi http://dx.doi.org/10.3390/cancers12092638
Klíčová slova breast cancer; lymph node; distant metastasis; GSEA; pathway; inhibitor
Popis 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. Our results indicate that lymph node positivity is associated with NF-kappa B and Src pathways and is related to high risk of distant metastasis in luminal A patients. Distant metastasis of lymph node negative tumors is related to cell proliferation control and thrombolysis, whereas distant metastasis of lymph node positive tumors is associated mostly to immune response. These mechanisms vary in other molecular subtypes. Our data indicate that the management of breast cancer and prevention of distant metastasis requires stratified approach based on targeted strategies. 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-kappa B 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 indicate that the management of breast cancer and prevention of distant metastasis requires stratified approach based on targeted strategies.
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