Mikkonen Jopi J W, Singh Surya P, Akhi Ramin, Salo Tuula, Lappalainen Reijo, González-Arriagada Wilfredo A, Ajudarte Lopes Márcio, Kullaa Arja M, Myllymaa Sami
SIB Labs, University of Eastern Finland, FI-70211 Kuopio, Finland.
Institute of Dentistry, University of Eastern Finland, FI-70211 Kuopio, Finland.
Oncol Lett. 2018 Nov;16(5):6795-6800. doi: 10.3892/ol.2018.9419. Epub 2018 Sep 7.
The analysis of the salivary metabolomic profile may offer an early phase approach to assess the changes associated with a wide range of diseases including head and neck cancer. The aim of the present study was to investigate the potential of nuclear magnetic resonance (NMR) spectroscopy for detecting the salivary metabolic changes associated with head and neck squamous cell carcinoma (HNSCC). Unstimulated whole-mouth saliva samples collected from HNSCC patients (primary tumour was located either in the larynx or in the oral cavity) and healthy controls were analysed by H-NMR spectroscopy. Reliably identified salivary metabolites were quantified and the determined concentration values were compared group-wise using a Mann-Whitney U-test. Multivariate discrimination function analysis (DFA) was conducted to identify such a combination of metabolites, when considered together, that gives maximum discrimination between the groups. HNSCC patients exhibited significantly increased concentrations of 1,2-propanediol (P=0.032) and fucose (P=0.003), while proline levels were significantly decreased (P=0.043). In the DFA model, the most powerful discrimination was achieved when fucose, glycine, methanol and proline were considered as combined biomarkers, resulting in a correct classification rate of 92.1%, sensitivity of 87.5% and specificity of 93.3%. To conclude, NMR spectrometric analysis was revealed to be a feasible approach to study the metabolome of saliva that is sensitive to metabolic changes in HNSCC and straightforward to collect in a non-invasive manner. Salivary fucose was of particular interest and therefore, controlled longitudinal studies are required to assess its clinical relevance as a diagnostic biomarker in HNSCC.
唾液代谢组学特征分析可能提供一种早期方法，用于评估与包括头颈癌在内的多种疾病相关的变化。本研究的目的是探讨核磁共振（NMR）光谱法检测与头颈部鳞状细胞癌（HNSCC）相关的唾液代谢变化的潜力。通过H-NMR光谱法分析了从HNSCC患者（原发肿瘤位于喉部或口腔）和健康对照者收集的非刺激性全口唾液样本。对可靠鉴定出的唾液代谢物进行定量，并使用曼-惠特尼U检验按组比较所确定的浓度值。进行多变量判别函数分析（DFA），以确定这样一组代谢物组合，当将它们一起考虑时，能在各组之间实现最大程度的区分。HNSCC患者的1,2-丙二醇浓度显著升高（P = 0.032）和岩藻糖浓度显著升高（P = 0.003），而脯氨酸水平显著降低（P = 0.043）。在DFA模型中，当将岩藻糖、甘氨酸、甲醇和脯氨酸作为联合生物标志物考虑时实现了最有力的区分，正确分类率为92.1%，灵敏度为87.5%，特异性为93.3%。总之，NMR光谱分析被证明是一种可行的方法，用于研究对HNSCC代谢变化敏感且易于以非侵入性方式收集的唾液代谢组。唾液岩藻糖特别受关注，因此需要进行对照纵向研究，以评估其作为HNSCC诊断生物标志物的临床相关性。
