Association of fatty acid binding protein 4 with altered immune composition and ferroptosis related signatures in metastatic medullary thyroid cancer
Year: 2026
Type: article
Study design: Observational Study
Abstract: Background: Medullary thyroid carcinoma (MTC) has a relatively poor prognosis mainly attributed to its early metastasis. This study aimed to investigate the expression pattern of fatty acid binding protein 4 (FABP4) and its relationship to the immune and metabolic landscape in metastatic MTC. Methods: Tissues for single-cell RNA sequencing (scRNA-seq) analysis were obtained from Jurong Hospital, to reveal the immune landscape of metastatic MTC. Gene expression profiles from Gene Expression Omnibus (GEO) were analyzed through weighted gene co-expression network analysis (WGCNA), differential expression gene (DEG) analysis and functional enrichment. Tissues for immunohistochemistry (IHC) were from The First Affiliated Hospital with Nanjing Medical University. Results: scRNA-seq showed that the lymph node cellular composition diverged from that of primary tissues, with an increased proportions of B cells versus T/natural killer cells. Gene set enrichment analysis (GSEA) revealed substantial enrichment pathways including fatty acid metabolism. After discriminating tumor cells by inferCNV and CopyKAT, FABP4 was more enriched in metastatic than in primary tumor cells, which was in line with IHC staining. Also, the module incorporating the six key genes including FABP4, which were found to be upregulated in metastatic MTC by DEGs with WGCNA. Functional enrichment displayed that the differential genes were associated with ferroptosis and fatty acid metabolism. The Cancer Genome Atlas (TCGA) data presented the correlation between FABP4 and glutathione peroxidase 4. Conclusions: Elevated FABP4 expression is associated with metastatic MTC, concurrent with altered immune cell composition and enrichment of ferroptosis related pathways. These findings identified FABP4 as a potential biomarker of metastasis, which is useful for the completement of theoretical basis and the guidance of personalized therapeutic strategies.
Source: Translational Cancer Research
Authors: Xiu Chen, Ying Yang, Yuxin Song, Hui Lu, Rong Fu
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W7224094234