Department of Chemistry and Biophysics, University of Michigan, Ann Arbor, MI, USA.
J Proteome Res. 2011 Nov 4;10(11):5232-41. doi: 10.1021/pr200800w. Epub 2011 Oct 18.
High-resolution magic-angle spinning (HR-MAS) proton NMR spectroscopy is used to explore the metabolic signatures of head and neck squamous cell carcinoma (HNSCC) which included matched normal adjacent tissue (NAT) and tumor originating from tongue, lip, larynx and oral cavity, and associated lymph-node metastatic (LN-Met) tissues. A total of 43 tissues (18 NAT, 18 Tumor and 7 LN-Met) from 22 HNSCC patients were analyzed. Principal Component Analysis of NMR data showed a clear classification between NAT and tumor tissues, however, LN-Met tissues were classified among tumor. A partial least-squares discriminant analysis model generated from NMR metabolic profiles was used to differentiate normal from tumor samples (Q(2) > 0.80, Receiver Operator Characteristic area under the curve >0.86, using 7-fold cross validation). HNSCC and LN-Met tissues showed elevated levels of lactate, amino acids including leucine, isoleucine, valine, alanine, glutamine, glutamate, aspartate, glycine, phenylalanine and tyrosine, choline containing compounds, creatine, taurine, glutathione, and decreased levels of triglycerides. These elevated metabolites were associated with highly active glycolysis, increased amino acids influx (anaplerosis) into the TCA cycle, altered energy metabolism, membrane choline phospholipid metabolism, and oxidative and osmotic defense mechanisms. Moreover, decreased levels of triglycerides may indicate lipolysis followed by β-oxidation of fatty acids that may exist to deliver bioenergy for rapid tumor cell proliferation and growth.
高分辨率魔角旋转（HR-MAS）质子 NMR 光谱用于探索头颈部鳞状细胞癌（HNSCC）的代谢特征，其中包括匹配的正常相邻组织（NAT）和源自舌、唇、喉和口腔的肿瘤，以及相关的淋巴结转移性（LN-Met）组织。对 22 例 HNSCC 患者的 43 个组织（18 个 NAT、18 个肿瘤和 7 个 LN-Met）进行了分析。NMR 数据的主成分分析显示 NAT 和肿瘤组织之间存在明显的分类，然而，LN-Met 组织被归类为肿瘤。从 NMR 代谢谱生成的偏最小二乘判别分析模型用于区分正常和肿瘤样本（Q(2) > 0.80，接收器操作特征曲线下面积>0.86，使用 7 倍交叉验证）。HNSCC 和 LN-Met 组织中乳酸、亮氨酸、异亮氨酸、缬氨酸、丙氨酸、谷氨酰胺、谷氨酸、天冬氨酸、甘氨酸、苯丙氨酸和酪氨酸等氨基酸、胆碱化合物、肌酸、牛磺酸、谷胱甘肽的水平升高，甘油三酯水平降低。这些升高的代谢物与高度活跃的糖酵解、进入 TCA 循环的氨基酸流入（氨甲酰化）、改变的能量代谢、膜胆碱磷脂代谢以及氧化和渗透防御机制有关。此外，甘油三酯水平的降低可能表明脂肪分解后脂肪酸的β-氧化可能存在，以提供生物能量，促进肿瘤细胞的快速增殖和生长。
