Integrated Serum and Spatial Metabolomics Reveals Compartmentalized Metabolic Reprogramming and Ferroptosis Susceptibility in Nasopharyngeal Carcinoma
- 1Department of Radiation Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, NHC Key Laboratory of Cancer Metabolism, Fuma Road, Fuzhou 350014, China
- 2Department of Electronic Science, National Institute for Data Science in Health and Medicine, Xiamen University, Xiamen 361005, China
Abstract
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.
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BibTeX
@article{hong2026integrated,
title = {{Integrated Serum and Spatial Metabolomics Reveals Compartmentalized Metabolic Reprogramming and Ferroptosis Susceptibility in Nasopharyngeal Carcinoma}},
author = {Huiling Hong and Yusong Zhang and Linhui Yan and Ting Xu and Yiying Xu and Zhaodong Fei and Jiyang Dong and Chuanben Chen},
journal = {Metabolites},
year = {2026},
month = oct,
doi = {10.3390/metabo16100783},
url = {https://www.mdpi.com/2218-1989/16/10/783},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Integrated Serum and Spatial Metabolomics Reveals Compartmentalized Metabolic Reprogramming and Ferroptosis Susceptibility in Nasopharyngeal Carcinoma
AU - Huiling Hong
AU - Yusong Zhang
AU - Linhui Yan
AU - Ting Xu
AU - Yiying Xu
AU - Zhaodong Fei
AU - Jiyang Dong
AU - Chuanben Chen
PY - 2026
DA - 2026/10/01
JO - Metabolites
DO - 10.3390/metabo16100783
UR - https://www.mdpi.com/2218-1989/16/10/783
AB - 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.
SN - 2218-1989
ER -