Chen Xi, Song Fei, Xiao Peng, Yao Yisong, Li Dongxian, Fang Yuhui, Lv Shijun, Mou Yakui, Li Yumei, Song Xicheng
Department of Otorhinolaryngology, Head and Neck Surgery, Yantai Yuhuangding Hospital, Qingdao University, Yantai, Shandong, 264000, China.
Shandong Provincial Key Laboratory of Neuroimmune Interaction and Regulation, Yantai, Shandong, 264000, China.
BMC Cancer. 2025 Mar 5;25(1):402. doi: 10.1186/s12885-025-13820-x.
Head and neck squamous cell carcinoma (HNSCC) is among the most aggressive malignancies, underscoring the need for early diagnosis to improve patient outcomes. Tumor-derived exosomes, which can be non-invasively obtained and reflect the metabolic state of tumors in real-time, are under increasing investigation for their diagnostic potential. Herein we analyzed metabolite differences in exosomes, serum, and tissues from patients with HNSCC to identify potential diagnostic biomarkers of clinical relevance.
Non-targeted metabolomics based on liquid chromatography-mass spectrometry was employed to quantify metabolites in exosome, serum, and tissue samples from 11 patients with HNSCC and six patients without cancer. The metabolic profiles of HNSCC were analyzed through univariate and multivariate statistical methods, differential metabolite analysis, and pathway enrichment analysis.
We identified three differential metabolites in exosomes, 45 in serum, and 33 in tissues. Notably, patients with HNSCC exhibited significant disruptions in protein and amino acid metabolism. Spermine was exclusively detected in exosomes and tissues from patients with HNSCC. We hypothesize that spermine is extracellularly secreted by malignant cells via exosomes and subsequently enters the bloodstream. Moreover, spermine synthase was highly expressed in HNSCC tissues. Knocking down spermine synthase markedly impaired HNSCC cell proliferation and migration.
This study provides a preliminarily characterization of the metabolic profile of HNSCC and highlights spermine and its synthetic pathways as potential diagnostic and therapeutic targets. Future studies are warranted to elucidate the mechanism of action of spermine in HNSCC and explore its utility in early diagnosis and therapeutic development.
头颈部鳞状细胞癌（HNSCC）是最具侵袭性的恶性肿瘤之一，这凸显了早期诊断以改善患者预后的必要性。肿瘤来源的外泌体可以通过非侵入性获取并实时反映肿瘤的代谢状态，其诊断潜力正受到越来越多的研究。在此，我们分析了HNSCC患者外泌体、血清和组织中的代谢物差异，以确定具有临床相关性的潜在诊断生物标志物。
采用基于液相色谱-质谱联用的非靶向代谢组学方法，对11例HNSCC患者和6例无癌患者的外泌体、血清和组织样本中的代谢物进行定量分析。通过单变量和多变量统计方法、差异代谢物分析和通路富集分析，对HNSCC的代谢谱进行分析。
我们在外泌体中鉴定出3种差异代谢物，血清中45种，组织中33种。值得注意的是，HNSCC患者在蛋白质和氨基酸代谢方面表现出显著紊乱。精胺仅在HNSCC患者的外泌体和组织中检测到。我们推测精胺由恶性细胞通过外泌体分泌到细胞外，随后进入血液循环。此外，精胺合酶在HNSCC组织中高表达。敲低精胺合酶显著损害HNSCC细胞的增殖和迁移。
本研究初步描绘了HNSCC的代谢谱，并突出了精胺及其合成途径作为潜在的诊断和治疗靶点。未来有必要开展研究以阐明精胺在HNSCC中的作用机制，并探索其在早期诊断和治疗开发中的应用价值。
