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Differential impact of classical and non-canonical NF-?B pathway-related gene expression on the survival of breast cancer patients.

ABSTRACT: Inflammation is a well-known driver of carcinogenesis and cancer progression, often attributed to the tumor microenvironment. However, tumor cells themselves are capable of secreting a variety of inflammatory molecules, leading to the activation of specific signaling pathways that promote tumor progression. The NF-?B signaling pathway is one of the most important connections between inflammation and tumorigenesis. NF-?B is a superfamily of transcription factors that plays an important role in several types of hematological and solid tumors, including breast cancer. However, the role of the NF-?B pathway in the survival of breast cancer patients is poorly studied. In this study, we analyzed and related the expression of both canonical and alternative NF-?B pathways and selected target genes with the relapse-free and overall survival of breast cancer patients. We used the public database Kaplan-Meier plotter (KMplot) which includes gene expression data and survival information of 3951 breast cancer patients. We found that the expression of IKK? 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 IKK?, 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. Our study suggests that the expression of genes of the canonical and alternative NF-?B pathways is ultimately critical for tumor persistence. Understanding the communication between both pathways would help to find better therapeutic and prophylactic targets to prevent breast cancer progression and relapse.

SUBMITTER: Espinoza-Sanchez NA 

PROVIDER: S-EPMC6775609 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Differential impact of classical and non-canonical NF-κB pathway-related gene expression on the survival of breast cancer patients.

Espinoza-Sánchez Nancy Adriana NA   Győrffy Balázs B   Fuentes-Pananá Ezequiel M EM   Götte Martin M  

Journal of Cancer 20190828 21

Inflammation is a well-known driver of carcinogenesis and cancer progression, often attributed to the tumor microenvironment. However, tumor cells themselves are capable of secreting a variety of inflammatory molecules, leading to the activation of specific signaling pathways that promote tumor progression. The NF-κB signaling pathway is one of the most important connections between inflammation and tumorigenesis. NF-κB is a superfamily of transcription factors that plays an important role in se  ...[more]

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