| [Purpose] To characterize plasma lipid profiles associated with different stages of esophageal squamous epithelial lesions using high-throughput lipidomics.
[Methods] This retrospective case-control study included 124 participants recruited from an organized esophageal cancer screening program conducted in Wenshang County, Shandong Province, between 2021 and 2023. The study population comprised 61 normal controls, 38 individuals with low-grade intraepithelial neoplasia (LGIN), and 25 with high-grade intraepithelial neoplasia (HGIN) or esophageal squamous cell carcinoma (ESCC). Untargeted lipidomic profiling was performed on plasma samples using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Partial least squares discriminant analysis and orthogonal partial least squares discriminant analysis were used to assess differences in lipid profiles among the study groups. Candidate lipid features associated with LGIN progression were identified by integrating variable importance in projection scores, fold changes, and results from age- and sex-adjusted logistic regression analyses.
[Results] High-throughput untargeted lipidomic profiling identified 2 284 lipid features spanning five major lipid categories and 51 subclasses. Sphingolipids, glycerophospholipids and glycerolipids were the most represented lipid categories, accounting for 32.0%, 30.5% and 21.4% of the lipid features, respectively. Across the normal control, LGIN, and HGIN/ESCC groups, ceramides showed an overall increase in relative abundance, whereas fatty acids showed an overall decrease. The relative abundances of phosphatidylcholines (PC), phosphatidylethanolamines, phosphatidylserines and triacylglycerols (TG) were higher in LGIN than in normal controls but lower in HGIN/ESCC than in LGIN. Among 25 differential lipid features that were lower in HGIN/ESCC than in LGIN, PC and TG were the predominant subclasses, with lysophosphatidylcholines (LPC) and diacylglycerols (DG) also represented; individual lipid species included PC 14:0_18:2 (odds ratio [OR]=0.15), PC 14:0_20:4 (OR=0.18), TG 14:0_18:2_22:6 (OR=0.18), TG 14:1_16:1_18:2 (OR=0.24), LPC 20:5 (OR=0.22) and DG 16:0_18:1 (OR=0.32).
[Conclusion] Plasma lipid profiles differed across different stages of esophageal squamous epithelial lesions. Lower relative abundances of lipids such as PC and TG may be associated with LGIN progression, but their potential for risk stratification needs to be validated in prospective studies. |
