Background:
Inflammation is a well-known driver of carcinogenesis and cancer progression, often
attributed to the tumor microenvironment. The NF-κB signaling pathway is an important
connection between inflammation and tumorigenesis. However, the role of the NF-κB
pathway in the survival of breast cancer patients is only poorly studied. In this
study, we analyzed and related the expression of both canonical and alternative NF-κB
pathways and selected target genes with the relapse-free and overall survival of breast
cancer patients.
Methods:
We used the transcriptomics-based public dataset of the Kaplan-Meier plotter (kmplot)
to determine overall survival (OS) and relapse-free survival (RFS) of 3951 breast
cancer patients. Gene expression was also determined by qPCR in a set of 7 breast
cancer cell lines representative of different molecular subtypes.
Results:
The expression of IKKα was associated with poor relapse-free survival in patients with ER-positive tumors.
Moreover, the expression of IL-8 and MMP-1 was associated with poor relapse-free and overall survival. In contrast, expression
of IKKβ, p50, and p65 from the canonical pathway, and NIK and RELB from the alternative pathway correlated with better relapse-free survival also when
the patients were classified by their hormonal and nodal status. Expression data in
cell lines revealed association of some NF-κB pathway compounds with a more aggressive
phenotype.
Conclusions:
Our study suggests that activation of the canonical and alternative NF-κB pathways
is ultimately critical for tumor survival. Understanding the communication between
both pathways would help to find better therapeutic and prophylactic targets to prevent
breast cancer progression and relapse.
