Fatty acid desaturase 1 drives esophageal cancer via M1 macrophage ferroptosis and lipid metabolism remodeling

doi:10.4251/wjgo.124110

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World Journal of Gastrointestinal Oncology

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1948-5204

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.

World J Gastrointest Oncol. Nov 15, 2026; 18(11): 124110
Published online Nov 15, 2026. doi: 10.4251/wjgo.124110

Table 1 Mendelian randomization estimates for the causal associations of five ferroptosis-related genes with esophageal cancer risk using the inverse variance weighted method

ID	NSNP	Method	β	SE	OR	OR_lci95	OR_uci95	P value
FADS2	14	IVW	-0.172	0.051	0.842	0.763	0.930	0.0007
FADS1	9	IVW	-0.282	0.097	0.755	0.624	0.913	0.0038
SRC	3	IVW	-2.202	0.951	0.111	0.017	0.713	0.0206
ELOVL5	3	IVW	0.492	0.237	1.635	1.027	2.603	0.0384
PPARG	7	IVW	-0.470	0.234	0.625	0.395	0.989	0.0445

FADS2: Fatty acid desaturase 2; FADS1: Fatty acid desaturase 1; SRC: SRC proto-oncogene, non-receptor tyrosine kinase; ELOVL5: Elongation of very long chain fatty acids protein 5; PPARG: Peroxisome proliferator-activated receptor gamma; IVW: Inverse variance weighted; NSNP: Number of single nucleotide polymorphisms; OR_lci95: Odds ratio lower 95% confidence interval; OR_uci95: Odds ratio upper 95% confidence interval.

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Table 2 Key mediator metabolites identified in the fatty acid desaturase 1-mediated metabolic pathway analysis

Metabolite	β₁	β₂	Mediation effect (β₁ × β₂)	Mediation proportion	P value
1-linoleoyl-GPE (18:2)	0.446	-0.285	-0.127	45.12%	0.006385603
1,2-dilinoleoyl-GPC (18:2/18:2)	0.451	-0.280	-0.126	44.84%	0.006059174
1-palmitoyl-2-stearoyl-gpc (16:0/18:0)	-0.399	0.449	-0.179	63.64%	0.006666497
1-stearoyl-2-arachidonoyl-GPE (18:0/20:4)	-0.392	0.294	-0.116	41.04%	0.000979761
1-linoleoyl-2-arachidonoyl-GPC (18:2/20:4n-6)	-0.559	0.240	-0.134	47.61%	0.000806059

β₁: Effect of fatty acid desaturase 1 on metabolite (inverse variance weighted); β₂: Effect of metabolite on esophageal cancer risk (inverse variance weighted); mediation effect = β₁ × β₂; mediation proportion = (mediation effect/total effect) × 100%; P value from the delta method (two-sided); GPE: Glycerophosphoethanolamine; GPC: Glycerophosphocholine.

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Table 3 Molecular docking results of the candidate compound BRD-K95779464 with the fatty acid desaturase 1protein

CurPocket ID	Vina score	Cavity volume (Å³)	Center (X, Y, Z)	Docking size (X, Y, Z)
C1	-8.3	5051	(-4, 8, -1)	(28, 28, 35)
C5	-8.1	163	(-8, -12, 13)	(22, 22, 22)
C2	-7.6	358	(-2, -5, -16)	(22, 22, 22)
C3	-6.2	203	(14, 13, 9)	(22, 22, 22)
C4	-5.7	186	(7, 8, -23)	(22, 22, 22)

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Citation: Du QC, Bai Y, Zhou DH, Yu H, Nian H. Fatty acid desaturase 1 drives esophageal cancer via M1 macrophage ferroptosis and lipid metabolism remodeling. World J Gastrointest Oncol 2026; 18(11): 124110
URL: https://www.wjgnet.com/1948-5204/full/v18/i11/124110.htm
DOI: https://dx.doi.org/10.4251/wjgo.124110

Du QC, Bai Y, Zhou DH, Yu H, Nian H. Fatty acid desaturase 1 drives esophageal cancer via M1 macrophage ferroptosis and lipid metabolism remodeling. World J Gastrointest Oncol 2026; 18(11): 124110 [DOI: 10.4251/wjgo.124110]

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