Metabolomic biomarkers associated with trismus and dysphagia, radiation therapy, tumour stage and location in patients with head and neck cancer

Trismus, difficulty opening the jaw, and dysphagia, difficulty swallowing, are complications in head and neck cancer (HNC). Metabolic imbalances, including alterations in amino acids, lipids, and inflammatory markers, potentially influence these conditions. The aim of this study was to investigate associations of metabolic and inflammatory metabolites in HNC patients, focusing on trismus and dysphagia. Nuclear Magnetic Resonance (NMR) spectroscopy, and Bruker IVDr Lipoprotein Subclass analysis was used to analyse metabolites in plasma from 302 patients before, during and after treatment for HNC. Sixteen lipoprotein subclasses (LDL 1–6, HDL 1–4 VLDL 1–6) as well as creatinine, creatine, glutamine, alanine, glycine, GlycA, GlycB, and a combined lipoprotein-derived NMR signal named Supramolecular Phospholipid Composite (SPC), were analysed. An increase in several lipoprotein sub fractions and elevated inflammatory biomarkers (GlycA and GlycB) were associated with Maximal Interincisal Opening (MIO) before treatment. The M.D. Anderson Dysphagia Inventory (MDADI) before treatment was associated with elevated GlycA and GlycB. The results also showed significant correlations between metabolites and BMI, sex, age, radiation therapy as well as tumour stage and location. Metabolic and inflammatory markers highlight the metabolic heterogeneity in HNC and provide potential targets for future therapeutic strategies.

牙关紧闭（Trismus）、张口困难以及吞咽困难（dysphagia）均为头颈癌（Head and Neck Cancer, HNC）患者的并发症。包括氨基酸、脂质及炎症标志物异常在内的代谢失衡，可能对上述病症产生影响。本研究旨在探究头颈癌患者体内代谢与炎症代谢物的关联，重点聚焦于牙关紧闭与吞咽困难。本研究采用核磁共振波谱法（Nuclear Magnetic Resonance, NMR）与布鲁克IVDr脂蛋白亚类分析技术，对302例头颈癌患者在治疗前、治疗中及治疗后采集的血浆样本中的代谢物进行检测分析。本次检测共分析了16种脂蛋白亚类（低密度脂蛋白（LDL）1-6、高密度脂蛋白（HDL）1-4、极低密度脂蛋白（VLDL）1-6），以及肌酐、肌酸、谷氨酰胺、丙氨酸、甘氨酸、GlycA、GlycB，还有一种由脂蛋白衍生的复合核磁共振信号——超分子磷脂复合物（Supramolecular Phospholipid Composite, SPC）。治疗前，多种脂蛋白亚组分水平升高与炎症生物标志物GlycA、GlycB水平上升，均与最大切牙开口度（Maximal Interincisal Opening, MIO）存在关联。治疗前的安德森吞咽困难量表（M.D. Anderson Dysphagia Inventory, MDADI）评分与GlycA、GlycB水平升高存在显著关联。研究结果还显示，代谢物水平与体重指数（BMI）、性别、年龄、放射治疗以及肿瘤分期与肿瘤部位均存在显著相关性。代谢与炎症标志物凸显了头颈癌的代谢异质性，并为未来的治疗策略提供了潜在靶点。