NF-κB Mediated Thyroid Inflammation and Its Implications for the Risk of Follicular Thyroid Carcinoma: a systematic review

Abstract

AbstractObjectiveThe objective of this study is to determine how NF-κB-mediated inflammation disrupts thyroid specific genes/TFs/signaling pathways and the resultant increase in the risk of Follicular Thyroid Carcinoma.BackgroundThyroid follicular carcinoma (FTC) is linked to chronic inflammation and NF-κB activation, which disrupts key thyroid-specific genes/transcription factors and signaling pathways. This dysregulation leads to impaired differentiation and increased proliferation, fostering oncogenesis. The interplay between NF-κB and thyroid components is critical for developing possible targeted therapies. This study aims to focus on these mechanisms, with the future potential of possibly improving diagnostic, prognostic, and therapeutic strategies for FTC.MethodsDatabases, including PubMed, MEDLINE, Google Scholar, and open access/ subscription-based journals were searched for published articles without any date restrictions, to investigate how NF-κB-mediated inflammation disrupts thyroid specific genes/TFs/signaling pathways and the resultant increase in the risk of Follicular Thyroid Carcinoma. Based on the criteria mentioned in the methods section, studies were systematically reviewed to investigate the research question. This study adheres to relevant PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses).ResultsNF-κB activation disrupts key thyroid transcription factors and signaling pathways, leading to increased risk of thyroid follicular carcinoma. Dysregulation of NKX2-1, PAX8, FOXE1, and HHEX impairs thyroid development and differentiation. NF-κB alters TSH signaling and disrupts RET/PTC, leading to aberrant cell proliferation. It further impacts the MAPK/ERK, PI3K/AKT, and Wnt/β- catenin pathways, driving oncogenic transformations. Additionally, NF-κB-induced changes in FGF, Shh, BMP, Notch, and TGF beta pathways exacerbate tumorigenesis by promoting abnormal cell growth and survival, collectively increasing follicular carcinoma risk.ConclusionChronic inflammation and NF-κB activation disrupt key transcription factors (NKX2-1, PAX8, FOXE1, HHEX) and signaling pathways (TSH, RET/PTC, MAPK/ERK, PI3K/AKT, Wnt/β-catenin, FGF, Shh, BMP, Notch, TGF-β) essential for thyroid development and function. This dysregulation leads to impaired differentiation, increased proliferation, and enhanced survival of thyroid follicular cells, fostering genomic instability and oncogenic transformation. These findings highlight the role of NF-κB in promoting follicular thyroid carcinoma (FTC) and points towards the need for targeted therapies to restore normal signaling and prevent malignancy in thyroid diseases.