ArticleAnnals of hematology2025
Serum triglyceride and apolipoprotein A1 as dynamic biomarkers in extranodal NK/T-cell lymphoma (ENKTL): A multicenter retrospective and prospective validation study.
Article in Annals of hematology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Extranodal NK/T-cell lymphoma (ENKTL), an aggressive non-Hodgkin lymphoma subtype, exhibits understudied links between lipid metabolism and clinical outcomes. We analyzed 1,017 patients newly diagnosed with ENKTL and matched controls, with longitudinal LC-MS-based metabolomic profiling (n = 29) and pretreatment tumor transcriptomic analysis (n = 65). Multivariable Cox models evaluated lipid biomarkers. Patients with ENKTL showed significantly elevated triglycerides (TG) and reduced apolipoprotein A1 (ApoA1) vs. controls (both p < 0.001). Elevated TG (progression-free survival [PFS] HR = 1.33, 95% CI 1.04-1.69; overall survival [OS] HR = 1.37, 95% CI 1.04-1.80) and reduced ApoA1 (PFS HR = 1.47, 95% CI 1.07-2.03; OS HR = 1.65, 95% CI 1.15-2.38) independently predicted inferior survival (all p < 0.05). Patients with an objective response demonstrated metabolic profile normalization: patients with high-TG levels (≥ median) experienced TG reduction and patients with low-ApoA1 levels (< median) experienced ApoA1 elevation (both p < 0.001), whereas patients with stable or progressive disease retained baseline profiles. These metabolic shifts predicted survival benefit (all p < 0.001). In the prospective cohort, patients with complete response (CR) had significantly higher baseline levels of 22 serum TG species compared with non-CR patients (fold change > 2.0, p < 0.05). Longitudinal analyses revealed divergent TG trajectories: patients without CR exhibited sustained high-level fluctuations, whereas patients with CR demonstrated stabilization at low levels. Transcriptome analysis suggested tumor-intrinsic lipid dysregulation in patients with high-TG/low-ApoA1 levels. Serum TG and ApoA1 serve as dynamic biomarkers in ENKTL.
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