State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, 17#, 3rd Section, Ren min South Road, Chengdu 610041, China.
Mol Cancer. 2013 Oct 18;12(1):121. doi: 10.1186/1476-4598-12-121.
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.
直肠癌是最常见的肿瘤类型之一。了解直肠癌的代谢特征对于开发治疗方法和分子诊断至关重要。
在这里，我们报告了使用基于 1H 核磁共振（1H NMR）的代谢组学分析方法对大量直肠癌患者（n=127）和正常对照（n=43）的组织样本进行的代谢组学分析。该方法是一种高度敏感和非破坏性的生物系统生物标志物鉴定方法。主成分分析（PCA）、偏最小二乘判别分析（PLS-DA）和正交偏最小二乘判别分析（OPLS-DA）用于分析 1H-NMR 图谱数据，以识别直肠癌的区别代谢物。
在不同阶段的直肠癌组织（I 期=35；II 期=37；III 期=37；IV 期=18）和正常对照组之间获得了极好的分离，并观察到了区别代谢物。共鉴定出 38 种差异代谢物，其中 16 种与直肠癌的分期密切相关。在癌症组织中检测到 10 种代谢物上调，包括乳酸、苏氨酸、乙酸盐、谷胱甘肽、尿嘧啶、琥珀酸盐、丝氨酸、甲酸盐、赖氨酸和酪氨酸。另一方面，癌症组织中 6 种代谢物（肌醇、牛磺酸、磷酸肌酸、肌酸、甜菜碱和二甲甘氨酸）减少。这些修饰的代谢物显示能量、氨基酸、酮体和胆碱代谢紊乱，这可能与人类直肠癌的进展有关。
我们的研究结果首次鉴定了不同阶段直肠癌组织中的区别代谢物，表明代谢物紊乱与直肠癌的进展有关。改变的代谢物可能是潜在的生物标志物，为人类直肠癌的临床诊断提供了有前途的分子诊断方法。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。
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