Magic angle spinning NMR-based metabolic profiling of head and neck squamous cell carcinoma tissues.

Magic angle spinning NMR-based metabolic profiling of head and neck squamous cell carcinoma tissues.
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DOI:
10.1021/pr200800w
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发表时间:
2011-11-04
影响因子:
4.4
通讯作者:
Ramamoorthy, Ayyalusamy
Ramamoorthy, Ayyalusamy
中科院分区:
生物学2区
文献类型:
--
作者:
Somashekar, Bagganahalli S.;Kamarajan, Pachiyappan;Danciu, Theodora;Kapila, Yvonne L.;Chinnaiyan, Arul M.;Rajendiran, Thekkelnaycke M.;Ramamoorthy, Ayyalusamy

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采用高分辨魔角旋转(HR-MAS)质子核磁共振波谱技术研究头颈部鳞状细胞癌(HNSCC)的代谢特征,包括匹配的正常邻近组织(NAT)和起源于舌、唇、喉和口腔的肿瘤,以及相关的淋巴结转移(LN-Met)组织。分析了来自22名HNSCC患者的总共43个组织(18个NAT、18个肿瘤和7个LN-Met)。主成分分析显示NAT和肿瘤组织之间有明确的分类,而LN-Met组织被归类为肿瘤。使用由NMR代谢谱产生的偏最小二乘判别分析模型来区分正常与肿瘤样品(Q2 > 0.80,曲线下接受者操作者特征面积> 0.80)。86,使用7折交叉验证)。HNSCC和LN-Met组织显示乳酸盐、氨基酸(包括亮氨酸、异亮氨酸、缬氨酸、丙氨酸、谷氨酰胺、谷氨酸盐、天冬氨酸盐、甘氨酸、苯丙氨酸和酪氨酸)、含胆碱化合物、肌酸、牛磺酸、谷胱甘肽水平升高,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、增加的氨基酸流入(回补)进入TCA循环、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相关。此外,甘油三酯水平降低可能表明脂肪分解,随后可能存在脂肪酸的β-氧化,以递送生物能量用于快速肿瘤细胞增殖和生长。
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 twenty-two 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 (Q2 > 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.
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