¹H NMR-based metabolic profiling of human rectal cancer tissue.
¹H NMR-based metabolic profiling of human rectal cancer tissue.
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DOI：
10.1186/1476-4598-12-121
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发表时间：
2013-10-18
期刊：
影响因子：
37.3
通讯作者：
Zhao YL
中科院分区：
文献类型：
--
作者：
Wang H;Wang L;Zhang H;Deng P;Chen J;Zhou B;Hu J;Zou J;Lu W;Xiang P;Wu T;Shao X;Li Y;Zhou Z;Zhao YL
直肠癌是最常见的肿瘤类型之一。了解直肠癌的代谢谱对于发展治疗方法和分子诊断是重要的。在这里，我们报告了一项基于1H核磁共振（1H NMR）的代谢组学分析，对一大批人类直肠癌受试者（n = 127）和正常对照（n = 43）的组织样本进行了代谢组学分析，这是一种在生物系统中识别生物标志物的高度敏感和非破坏性的方法。采用主成分分析（PCA）、偏最小二乘判别分析（PLS-DA）和正交投影到潜在结构判别分析（OPLS-DA）对1H-NMR谱分析数据进行分析，以确定直肠癌的鉴别代谢物。在不同分期的直肠癌组织（I期35例，II期37例，III期37例，IV期18例）和正常对照中，获得了很好的分离，代谢物也很明显。共鉴定出38种差异代谢物，其中16种与直肠癌分期密切相关。癌组织中乳酸、苏氨酸、乙酸、谷胱甘肽、尿嘧啶、琥珀酸、丝氨酸、甲酸、赖氨酸和酪氨酸等10种代谢物表达上调。另一方面，癌组织中肌醇、牛磺酸、磷酸肌酸、肌酸、甜菜碱、二甲基甘氨酸等6种代谢物降低。这些修饰的代谢物显示了能量、氨基酸、酮体和胆碱代谢的紊乱，这可能与人类直肠癌的进展有关。我们的发现首次确定了不同阶段直肠癌组织中具有区别性的代谢物，提示代谢物紊乱可能与直肠癌的进展有关。这些改变的代谢产物可能作为潜在的生物标志物，为人类直肠癌的临床诊断提供一种有前景的分子诊断方法。代谢物在直肠癌进展中的作用和潜在机制值得进一步研究。
Rectal cancer is one of the most prevalent tumor types. Understanding the metabolic profile of rectal cancer is important for developing therapeutic approaches and molecular diagnosis. Here, we report a metabonomics profiling of tissue samples on a large cohort of human rectal cancer subjects (n = 127) and normal controls (n = 43) using 1H nuclear magnetic resonance (1H NMR) based metabonomics assay, which is a highly sensitive and non-destructive method for the biomarker identification in biological systems. Principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA) and orthogonal projection to latent structure with discriminant analysis (OPLS-DA) were applied to analyze the 1H-NMR profiling data to identify the distinguishing metabolites of rectal cancer. Excellent separation was obtained and distinguishing metabolites were observed among the different stages of rectal cancer tissues (stage I = 35; stage II = 37; stage III = 37 and stage IV = 18) and normal controls. A total of 38 differential metabolites were identified, 16 of which were closely correlated with the stage of rectal cancer. The up-regulation of 10 metabolites, including lactate, threonine, acetate, glutathione, uracil, succinate, serine, formate, lysine and tyrosine, were detected in the cancer tissues. On the other hand, 6 metabolites, including myo-inositol, taurine, phosphocreatine, creatine, betaine and dimethylglycine were decreased in cancer tissues. These modified metabolites revealed disturbance of energy, amino acids, ketone body and choline metabolism, which may be correlated with the progression of human rectal cancer. Our findings firstly identify the distinguishing metabolites in different stages of rectal cancer tissues, indicating possibility of the attribution of metabolites disturbance to the progression of rectal cancer. The altered metabolites may be as potential biomarkers, which would provide a promising molecular diagnostic approach for clinical diagnosis of human rectal cancer. The role and underlying mechanism of metabolites in rectal cancer progression are worth being further investigated.
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