整合血清与空间代谢组学揭示鼻咽癌中的区室化代谢重编程与铁死亡易感性

文献信息

中文摘要

背景： 鼻咽癌（NPC）是一种在中国南方高发的恶性肿瘤。代谢重编程是癌症的标志性特征，然而NPC全身与局部代谢景观之间的相互作用仍鲜有表征。本研究旨在通过整合代谢组学识别血清代谢生物标志物并刻画局部组织代谢改变。
方法： 我们开展了一项双区室代谢组学研究。对80例NPC患者和35例健康对照进行非靶向血清代谢组学分析。应用气流辅助解吸电喷雾电离质谱成像（AFADESI-MSI）分析鼻咽组织（3例NPC vs. 3例慢性炎症组织）。进行跨平台整合以识别重叠的代谢特征，随后采用最小绝对收缩和选择算子（LASSO）回归进行特征选择，并采用逻辑回归构建生物标志物组合。
结果： 血清代谢组学揭示涉及氨基酸和丙酸代谢的全身性扰动。空间代谢组学确定甘油磷脂代谢为NPC组织中改变最显著的途径，肿瘤区域磷脂酰丝氨酸显著降低，且铁死亡途径显著富集。跨组学整合识别出8种重叠代谢物，其中5种映射至不饱和脂肪酸生物合成。半胱氨酸表现出优异的诊断性能（受试者工作特征曲线下面积（AUC）= 0.903）。5种代谢物联合模型达到AUC 0.904（95%置信区间（CI）：0.892-0.916）。
结论： NPC表现出区室化代谢重编程，其特征为全身性氨基酸和丙酸扰动，同时伴有局部甘油磷脂重塑和铁死亡易感性。所识别的5种代谢物血清组合显示出作为NPC无创诊断工具的相当大的潜力。

英文摘要

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a malignancy highly prevalent in southern China. Metabolic reprogramming is a hallmark of cancer, yet the interplay between the systemic and local metabolic landscapes of NPC remains poorly characterized. This study aimed to identify serum metabolic biomarkers and characterize local tissue metabolic alterations through integrated metabolomics.
METHODS: We conducted a dual-compartment metabolomic investigation. Untargeted serum metabolomics was performed on 80 NPC patients and 35 healthy controls. Air flow-assisted desorption electrospray ionization mass spectrometry imaging (AFADESI-MSI) was applied to nasopharyngeal tissues (3 NPC vs. 3 chronically inflamed tissues). Cross-platform integration was performed to identify overlapping metabolic signatures, followed by least absolute shrinkage and selection operator (LASSO) regression for feature selection and logistic regression for biomarker panel construction.
RESULTS: Serum metabolomics revealed systemic perturbations involving amino acid and propanoate metabolism. Spatial metabolomics identified glycerophospholipid metabolism as the most significantly altered pathway in NPC tissues, with markedly reduced phosphatidylserine in tumor regions, and the ferroptosis pathway was significantly enriched. Cross-omics integration identified 8 overlapping metabolites, of which 5 were mapped to the biosynthesis of unsaturated fatty acids. Cysteine demonstrated excellent diagnostic performance (area under the receiver operating characteristic curve (AUC) = 0.903). A 5-metabolite combined model achieved an AUC of 0.904 (95% confidence interval (CI): 0.892-0.916).
CONCLUSIONS: NPC exhibits compartmentalized metabolic reprogramming characterized by systemic amino acid and propanoate perturbations alongside local glycerophospholipid remodeling and ferroptosis susceptibility. The identified 5-metabolite serum panel shows considerable potential as a non-invasive diagnostic tool for NPC.