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Peer-reviewedCC BY-NC-ND 4.0Translational Cancer Research

Association of fatty acid binding protein 4 with altered immune composition and ferroptosis related signatures in metastatic medullary thyroid cancer

  1. 1Department of General Surgery, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China
  2. 2Department of General Surgery, Yancheng First Hospital Affiliated of Nanjing University Medical College, Yancheng, China

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.

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BibTeX
@article{chen2026association,
  title = {{Association of fatty acid binding protein 4 with altered immune composition and ferroptosis related signatures in metastatic medullary thyroid cancer}},
  author = {Xiu Chen and Ying Yang and Yuxin Song and Hui Lu and Rong Fu},
  journal = {Translational Cancer Research},
  year = {2026},
  month = sep,
  doi = {10.21037/tcr-2026-1934},
  url = {https://doi.org/10.21037/tcr-2026-1934},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - Association of fatty acid binding protein 4 with altered immune composition and ferroptosis related signatures in metastatic medullary thyroid cancer
AU  - Xiu Chen
AU  - Ying Yang
AU  - Yuxin Song
AU  - Hui Lu
AU  - Rong Fu
PY  - 2026
DA  - 2026/09/28
JO  - Translational Cancer Research
DO  - 10.21037/tcr-2026-1934
UR  - https://doi.org/10.21037/tcr-2026-1934
AB  - 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.
SN  - 2218-676X
SN  - 2219-6803
ER  -