EBF1 modulates tumor metastasis and immune microenvironment via remodeling the extracellular matrix in thyroid cancer

ABSTRACT: Background: The rising incidence of thyroid cancer presents challenges related to metastasis and treatment resistance. While emerging immunotherapy shows promise, accurately identifying suitable patients remains difficult. Transcription factors are vital for signaling and gene regulation in normal cellular functions. Studying their dysregulation in thyroid cancer may uncover new biomarkers for treatment. Methods: Early B-cell factor 1 (EBF1) has been reported to involve in the progression of several tumor types, however the role of EBF1 in thyroid cancer was undetermined. To address this gap, EBF1 expression was assessed using the TCGA database and validated in thyroid cancer cell lines and tissue samples via Western blot. RT-qPCR confirmed the effects of epigenetic drugs on EBF1 expression and identified its silencing mechanism. Stable thyroid cell lines overexpressing EBF1 were constructed to verify its function on metastasis via cell migration, invasion and wound healing assays. RNA sequencing and RT-qPCR were performed to explore the downstream pathways and target genes. Bioinformatics algorithms, including ESTIMATE, TIDE, and ssGSEA, were used to clarify the relationship between EBF1 and the immune microenvironment. Single-cell analysis examined the localization of EBF1 and its target genes, revealing potential mechanisms for EBF1’s role in remodeling the immune microenvironment. Results: The results showed that EBF1 exhibited significant downregulation in thyroid cancer, particularly in anaplastic thyroid cancer (ATC). This downregulation did not correlate with DNA methylation; instead, it was associated with histone H3K27ac modifications. Overexpression of EBF1 upregulated genes involved in cell adhesion and ECM pathways, inhibiting cell migration and invasion. Furthermore, EBF1 was mainly expressed in endothelial cells and fibroblasts, and its diminished expression correlated with an immunosuppressive tumor microenvironment and a decreased infiltration of immune effector cells. Conclusion: In conclusion, this study identified EBF1 as a tumor suppressor in thyroid cancer. The loss of EBF1 may contribute to tumor cell metastasis or the establishment of an immunosuppressive microenvironment through its regulation of the extracellular matrix.

ORGANISM(S): Homo sapiens

PROVIDER: GSE349059 | GEO | 2026/09/29

REPOSITORIES: GEO