Nutrition-related lipid metabolism and ferroptosis in endometrial cancer: transcriptomic profiling and hypoxia-associated gene expression
4 affiliations
- 1Department of Gynecology, Yiwu Central Hospital
- 2Department of Obstetrics and Gynaecology, Huai'an Hospital of Huai'an City (Huai'an Clinical Medical College of Jiangsu University)
- 3Department of Obstetrics and Gynaecology, Handan Central Hospital
- 4Department of Pathology, Women's Hospital of Nanjing Medical University, Nanjing Women and Children's Healthcare Hospital
Abstract
Background: Endometrial cancer is closely linked to obesity, insulin resistance and nutrition-related metabolic dysfunction. We examined lipid-synthesis and ferroptosis-related programs across tumor cell states and assessed lipogenic and ferroptosis-regulatory gene expression under hypoxia.
Methods: Six single-cell RNA-sequencing libraries from three primary endometrial tumors and one Visium section were analyzed alongside 545 TCGA-UCEC tumors. Lipid-metabolism, ferroptosis, hypoxia and immune scores were evaluated at cellular, spatial and bulk-tissue levels. HEC-1-A and KLE cells were cultured under normoxia or hypoxia for 24 h, with three independent cultures per condition, and gene expression was assessed by qRT-PCR.
Results: After quality control and doublet removal, 4,167 cells were retained and assigned to 14 annotated populations. Epithelial cells had the highest median lipid-synthesis score. Among 1,273 epithelial-lineage cells, hypoxia was weakly correlated with the ferroptosis-driver score ( r = 0.091, FDR = 0.0096), but not with defense. Across 1,347 spatial spots, epithelial and lipid-synthesis scores were positively correlated ( r = 0.191, FDR = 1.5 × 10–11). TCGA resistance scores were lower in serous than endometrioid tumors and higher in MSI-H than MSS tumors. Resistance was not independently associated with overall survival (HR = 0.83, 95% CI 0.47–1.47) and was unrelated to BMI. Under hypoxia, SREBF1, FASN and SCD expression was higher in both cell lines, together with CA9, GPX4, SLC7A11, AIFM2 and ACSL4.
Conclusion: Lipid-synthesis and ferroptosis-related programs varied across endometrial-cancer cell states and tissue regions. Hypoxic cell models showed concurrent changes in lipogenic and ferroptosis-regulatory transcripts. These findings identify metabolic transcriptional responses for functional investigation, without establishing a dietary effect or independent prognostic value for the resistance score.
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BibTeX
@article{lou2026nutritionrelated,
title = {{Nutrition-related lipid metabolism and ferroptosis in endometrial cancer: transcriptomic profiling and hypoxia-associated gene expression}},
author = {Xiaozhen Lou and Weiwei Cai and Jingjing Wang and Jinrong Wu},
journal = {Frontiers in Public Health},
year = {2026},
month = nov,
doi = {10.3389/fpubh.2026.1991840},
url = {https://www.frontiersin.org/articles/10.3389/fpubh.2026.1991840/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Nutrition-related lipid metabolism and ferroptosis in endometrial cancer: transcriptomic profiling and hypoxia-associated gene expression
AU - Xiaozhen Lou
AU - Weiwei Cai
AU - Jingjing Wang
AU - Jinrong Wu
PY - 2026
DA - 2026/11/04
JO - Frontiers in Public Health
DO - 10.3389/fpubh.2026.1991840
UR - https://www.frontiersin.org/articles/10.3389/fpubh.2026.1991840/full
AB - Background: Endometrial cancer is closely linked to obesity, insulin resistance and nutrition-related metabolic dysfunction. We examined lipid-synthesis and ferroptosis-related programs across tumor cell states and assessed lipogenic and ferroptosis-regulatory gene expression under hypoxia. Methods: Six single-cell RNA-sequencing libraries from three primary endometrial tumors and one Visium section were analyzed alongside 545 TCGA-UCEC tumors. Lipid-metabolism, ferroptosis, hypoxia and immune scores were evaluated at cellular, spatial and bulk-tissue levels. HEC-1-A and KLE cells were cultured under normoxia or hypoxia for 24 h, with three independent cultures per condition, and gene expression was assessed by qRT-PCR. Results: After quality control and doublet removal, 4,167 cells were retained and assigned to 14 annotated populations. Epithelial cells had the highest median lipid-synthesis score. Among 1,273 epithelial-lineage cells, hypoxia was weakly correlated with the ferroptosis-driver score ( r = 0.091, FDR = 0.0096), but not with defense. Across 1,347 spatial spots, epithelial and lipid-synthesis scores were positively correlated ( r = 0.191, FDR = 1.5 × 10–11). TCGA resistance scores were lower in serous than endometrioid tumors and higher in MSI-H than MSS tumors. Resistance was not independently associated with overall survival (HR = 0.83, 95% CI 0.47–1.47) and was unrelated to BMI. Under hypoxia, SREBF1, FASN and SCD expression was higher in both cell lines, together with CA9, GPX4, SLC7A11, AIFM2 and ACSL4. Conclusion: Lipid-synthesis and ferroptosis-related programs varied across endometrial-cancer cell states and tissue regions. Hypoxic cell models showed concurrent changes in lipogenic and ferroptosis-regulatory transcripts. These findings identify metabolic transcriptional responses for functional investigation, without establishing a dietary effect or independent prognostic value for the resistance score.
SN - 2296-2565
ER -