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<p>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 (<i>n</i> = 29) and pretreatment tumor transcriptomic analysis (<i>n</i> = 65). Multivariable Cox models evaluated lipid biomarkers. Patients with ENKTL showed significantly elevated triglycerides (TG) and reduced apolipoprotein A1 (ApoA1) vs. controls (both <i>p</i> &lt; 0.001). Elevated TG (progression-free survival [PFS] HR = 1.33, 95% CI 1.04<b>–</b>1.69; overall survival [OS] HR = 1.37, 95% CI 1.04<b>–</b>1.80) and reduced ApoA1 (PFS HR = 1.47, 95% CI 1.07<b>–</b>2.03; OS HR = 1.65, 95% CI 1.15<b>–</b>2.38) independently predicted inferior survival (all <i>p</i> &lt; 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 (&lt; median) experienced ApoA1 elevation (both <i>p</i> &lt; 0.001), whereas patients with stable or progressive disease retained baseline profiles. These metabolic shifts predicted survival benefit (all <i>p</i> &lt; 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 &gt; 2.0, <i>p</i> &lt; 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.</p>

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Serum triglyceride and apolipoprotein A1 as dynamic biomarkers in extranodal NK/T-cell lymphoma (ENKTL): A multicenter retrospective and prospective validation study

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月17日

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  • Jin-Ni Wang,
  • Jie Xiong,
  • Han-Guo Guo,
  • Zhi-Hua Li,
  • Yi Cao,
  • Yu Fang,
  • Yu-Ying Liu,
  • Yan-Hong Li,
  • Jun Cai,
  • Yu-Chen Zhang,
  • Qi-Hua Zou,
  • Jia-Hui Wang,
  • Yi Xia,
  • Hui-Qiang Huang,
  • Chang-Gang Sun,
  • Song-Qi Li,
  • Liang Wang,
  • Wei-Li Zhao,
  • Qing-Qing Cai

摘要

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.