PO.CL01.16 · 临床研究

动态炎症生物标志物与前瞻性肺癌队列中的癌症恶病质相关

Dynamic inflammatory biomarkers are associated with cancer cachexia in a prospective lung cancer cohort

编号 3928 展板 3 时间 4/20 02:00–05:00 区域 Section 48 主讲 Elham Kazemian, PhD

分会场 Prognostic Biomarkers 2

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作者与单位 Authors & Affiliations

Elham Kazemian¹, Carlos David Cruz-Hernandez², Karen L. Reckamp¹, Puneeth Iyengar³, Neil A. Bhowmick⁴, Jane C. Figueiredo⁵, Kamya Sankar¹

¹Cedars-Sinai Medical Center, Los Angeles, CA,²Cedars-Sinai Medical Center, Beverly Hills, CA,³Memorial Sloan Kettering Cancer Center, New York, NY,⁴Assoc. Professor, Dept. of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA,⁵Samuel Oschin Comprehensive Cancer Institute, Los Angeles, CA

摘要 Abstract

中文摘要

背景：癌症恶病质是一种多因素综合征，以进行性骨骼肌丢失为特征，约影响40-50%的非小细胞肺癌（NSCLC）患者。尽管其临床影响显著，但用于早期检测和风险分层的可靠生物标志物仍未明确界定。方法：在这项前瞻性纵向研究中，我们对来自SeroNet-CORALE队列的27例IV期NSCLC患者进行了分析，这些患者在2020-2023年间至少采集了两份血浆样本。恶病质根据国际共识标准定义（6个月内体重下降>5%，或体重下降>2%且BMI<20 kg/m2）。我们使用MesoScale Discovery平台定量检测了40种生物标志物，包括炎症细胞因子、趋化因子、代谢激素、血管生成因子和线粒体DNA。采用Firth惩罚逻辑回归模型评估经log2转换的生物标志物水平与恶病质状态之间的关联，并对年龄、性别、种族和治疗暴露进行校正。结果：我们纳入了肺癌患者（65%为女性，平均年龄65±10岁），组织学以腺癌为主（89%），在诊断时被归类为恶病质的比例为22%，在随后的时间点分别为20%和19%。恶病质患者的BMI持续较低（T1时21.0±2.0对27.0±7.0；T2时21.8±4.9对25.2±4.9）。在T1时，恶病质与GDF15升高（OR：4.29，95% CI：1.04-29.74，p=0.044）和IL-15升高（OR：43.83，95% CI：2.39->999，p=0.007）密切相关，而IL-4表现出保护作用（OR：0.09，95% CI：0.00-0.66，p=0.013）。到T2时，生物标志物谱发生了变化，出现了与mtDNA升高（OR：2.13，95% CI：1.07-7.69，p=0.022）以及IL-5（OR：0.17，p=0.011）、IL12/IL23p40（OR：0.44，p=0.010）和MDC（OR：0.26，p=0.006）水平降低相关的显著关联。纵向分析显示，基线炎症生物标志物与未来恶病质风险相关。基线MCP-1升高显示出与6个月随访时恶病质几率增加相关的强烈但无统计学意义的趋势（OR：3.72，95% CI：0.91-42.70，p=0.070）。相反，基线时较高水平的MDC（OR：0.19，95% CI：0.02-0.77，p=0.016）和TARC（OR：0.28，95% CI：0.04-0.96，p=0.041）与随后时间点恶病质几率降低显著相关。结论：这项探索性研究揭示了与癌症恶病质相关的炎症谱的时间变化。尽管需要在更大的队列中进行验证，但不同时间点的独特生物标志物模式提示，恶病质的生物学过程可能从最初的细胞因子激活演变为后期的线粒体和免疫失调。基线生物标志物与未来恶病质发展之间的关联需谨慎解读，但可能为未来的研究方向提供参考。

查看英文原文 English abstract

Background: Cancer cachexia is a multifactorial syndrome characterized by progressive skeletal muscle loss that affects approximately 40-50% of patients with non-small cell lung cancer (NSCLC)Despite its clinical impact, reliable biomarkers for early detection and risk stratification remain poorly defined. Methods: In this prospective longitudinal study,we conducted an analysis of 27 patients with stage IV NSCLC from the SeroNet-CORALE cohort with at least two plasma samples collected between 2020-2023. Cachexia was defined according to international consensus criteria (weight loss >5% or >2% with BMI<20 kg/m2 over 6 months). We quantified 40 biomarkers using MesoScale Discovery platforms, including inflammatory cytokines, chemokines, metabolic hormones, angiogenic factors, and mitochondrial DNA. Firth penalized logistic regression models were used to evaluate associations between log2-transformed biomarker levels and cachexia status, with adjustment for age, sex, race, and treatment exposures. Results: We enrolled lung cancer patients (65% female, mean age 65±10 years) with predominantly adenocarcinoma histology (89 percent), and the proportion classified as cachectic was 22 percent at diagnosis and 20 percent and 19 percent at the subsequent timepoints. Cachectic patients showed consistently lower BMI (21.0±2.0 vs 27.0±7.0 at T1; 21.8±4.9 vs 25.2±4.9 at T2). At T1, cachexia was strongly associated with elevated GDF15 (OR: 4.29, 95% CI: 1.04-29.74, p=0.044) and IL-15 (OR: 43.83, 95% CI: 2.39->999, p=0.007), while IL-4 demonstrated protective effects (OR: 0.09, 95% CI: 0.00-0.66, p=0.013). By T2, the biomarker profile had shifted, with significant associations emerging for elevated mtDNA (OR: 2.13, 95% CI: 1.07-7.69, p=0.022) and reduced levels of IL-5 (OR: 0.17, p=0.011), IL12/IL23p40 (OR: 0.44, p=0.010), and MDC (OR: 0.26, p=0.006). Longitudinal analysis revealed that baseline inflammatory biomarkers were associated with future cachexia risk. Elevated MCP-1 at baseline showed a strong, though non-significant, trend toward association with increased odds of cachexia at the 6-month follow-up (OR: 3.72, 95% CI: 0.91-42.70, p=0.070). In contrast, higher levels of MDC (OR: 0.19, 95% CI: 0.02-0.77, p=0.016) and TARC (OR: 0.28, 95% CI: 0.04-0.96, p=0.041) at baseline were significantly associated with reduced odds of cachexia at the subsequent timepoint. Conclusion: This exploratory study reveals temporal variations in inflammatory profiles associated with cancer cachexia. While requiring validation in larger cohorts, the distinct biomarker patterns at different timepoints suggest cachexia biology may evolve from initial cytokine activation to later-stage mitochondrial and immune dysregulation. The association between baseline biomarkers and future cachexia development warrants cautious interpretation but may inform future research directions.

利益披露 Disclosure

E. Kazemian, None.

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