Department of Clinical Laboratory, Wuzhou Red Cross Hospital, Wuzhou, Guangxi, China.
Guangxi Health Commission Key Laboratory of Molecular Epidemiology of Nasopharyngeal Carcinoma, Wuzhou Red Cross Hospital, Wuzhou, Guangxi, China.
Front Immunol. 2024 Apr 26;15:1375931. doi: 10.3389/fimmu.2024.1375931. eCollection 2024.
This study aimed to establish an effective prognostic model based on triglyceride and inflammatory markers, including neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR), to predict overall survival (OS) in patients with nasopharyngeal carcinoma (NPC). Additionally, we aimed to explore the interaction and mediation between these biomarkers in their association with OS.
A retrospective review was conducted on 259 NPC patients who had blood lipid markers, including triglyceride and total cholesterol, as well as parameters of peripheral blood cells measured before treatment. These patients were followed up for over 5 years, and randomly divided into a training set (n=155) and a validation set (n=104). The triglyceride-inflammation (TI) score was developed using the random survival forest (RSF) algorithm. Subsequently, a nomogram was created. The performance of the prognostic model was measured by the concordance index (C-index), time-dependent receiver operating characteristic (ROC) curve, and decision curve analysis (DCA). The interaction and mediation between the biomarkers were further analyzed. Bioinformatics analysis based on the GEO dataset was used to investigate the association between triglyceride metabolism and immune cell infiltration.
The C-index of the TI score was 0.806 in the training set, 0.759 in the validation set, and 0.808 in the entire set. The area under the curve of time-dependent ROC of TI score in predicting survival at 1, 3, and 5 years were 0.741, 0.847, and 0.871 respectively in the training set, and 0.811, 0.837, and 0.758 in the validation set, then 0.771, 0.848, and 0.862 in the entire set, suggesting that TI score had excellent performance in predicting OS in NPC patients. Patients with stage T1-T2 or M0 had significantly lower TI scores, NLR, and PLR, and higher LMR compared to those with stage T3-T3 or M1, respectively. The nomogram, which integrated age, sex, clinical stage, and TI score, demonstrated good clinical usefulness and predictive ability, as evaluated by the DCA. Significant interactions were found between triglyceride and NLR and platelet, but triglyceride did not exhibit any medicating effects in the inflammatory markers. Additionally, NPC tissues with active triglyceride synthesis exhibited high immune cell infiltration.
The TI score based on RSF represents a potential prognostic factor for NPC patients, offering convenience and economic advantages. The interaction between triglyceride and NLR may be attributed to the effect of triglyceride metabolism on immune response.
本研究旨在建立一个基于甘油三酯和炎症标志物(包括中性粒细胞与淋巴细胞比值[NLR]、淋巴细胞与单核细胞比值[LMR]和血小板与淋巴细胞比值[PLR])的有效预后模型,以预测鼻咽癌(NPC)患者的总生存期(OS)。此外,我们还旨在探讨这些生物标志物在与 OS 相关联时的相互作用和中介作用。
回顾性分析了 259 例 NPC 患者的血脂标志物,包括甘油三酯和总胆固醇,以及治疗前外周血细胞参数。这些患者的随访时间超过 5 年,并随机分为训练集(n=155)和验证集(n=104)。使用随机生存森林(RSF)算法构建甘油三酯-炎症(TI)评分。随后创建了一个列线图。通过一致性指数(C-index)、时间依赖性接收器工作特征(ROC)曲线和决策曲线分析(DCA)来衡量预后模型的性能。进一步分析了生物标志物之间的相互作用和中介作用。基于 GEO 数据集的生物信息学分析用于研究甘油三酯代谢与免疫细胞浸润之间的关系。
TI 评分在训练集的 C-index 为 0.806,在验证集为 0.759,在整个数据集为 0.808。TI 评分在预测 1、3 和 5 年生存时的时间依赖性 ROC 曲线下面积在训练集分别为 0.741、0.847 和 0.871,在验证集分别为 0.811、0.837 和 0.758,然后在整个数据集分别为 0.771、0.848 和 0.862,表明 TI 评分在预测 NPC 患者 OS 方面具有出色的性能。与 T3-T3 或 M1 期患者相比,T1-T2 或 M0 期患者的 TI 评分、NLR 和 PLR 显著降低,LMR 显著升高。整合年龄、性别、临床分期和 TI 评分的列线图,通过 DCA 评估显示出良好的临床实用性和预测能力。发现甘油三酯与 NLR 和血小板之间存在显著的相互作用,但甘油三酯在炎症标志物中没有表现出任何介导作用。此外,具有活跃甘油三酯合成的 NPC 组织表现出高免疫细胞浸润。
基于 RSF 的 TI 评分是 NPC 患者潜在的预后因素,具有方便和经济优势。甘油三酯与 NLR 之间的相互作用可能归因于甘油三酯代谢对免疫反应的影响。