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J Cancer. 2019 Aug 28;10(21):5191-5211. doi: 10.7150/jca.34302. eCollection 2019.

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

Author information

1
Unidad de Investigación en Virología y Cáncer, Hospital Infantil de México Federico Gómez, C.P. 06720, Ciudad de México, México.
2
MTA TTK Lendület Cancer Biomarker Research Group, Institute of Enzymology, Hungarian Academy of Sciences, and Semmelweis University 2nd Dept. of Pediatrics, Budapest, Hungary.
3
Department of Gynecology and Obstetrics, Münster University Hospital, Münster, Germany.

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-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 several types of hematological and solid tumors, including breast cancer. However, the role of the NF-κB 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-κB 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 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. Our study suggests that the expression of genes of the canonical and alternative NF-κB 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.

KEYWORDS:

Breast cancer; KM plotter.; NF-κB; inflammation; prognosis; survival analysis

Conflict of interest statement

Competing Interests: The authors have declared that no competing interest exists.

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