Pharmacodynamics Pharmacokinetics Early Safety Evaluation Model Animals, Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, Sichuan 610041, P.R. China.
Analytical and Testing Center, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
Oncol Rep. 2017 Nov;38(5):3044-3054. doi: 10.3892/or.2017.5954. Epub 2017 Sep 13.
Lung metastasis is an important cause for the low 5-year survival rate of colorectal cancer patients. Understanding the metabolic profile of lung metastasis of colorectal cancer is important for developing molecular diagnostic and therapeutic approaches. We carried out the metabonomic profiling of lung tissue samples on a mouse lung metastasis model of colorectal cancer using 1H-nuclear magnetic resonance (1H-NMR). The lung tissues of mice were collected at different intervals after marine colon cancer cell line CT-26 was intravenously injected into BALB/c mice. The distinguishing metabolites of lung tissue were investigated using 1H-NMR-based metabonomic assay, which is a highly sensitive and non-destructive method for biomarker identification. Principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were applied to analyze 1H-NMR profiling data to seek potential biomarkers. All of the 3 analyses achieved excellent separations between the normal and metastasis groups. A total of 42 metabolites were identified, ~12 of which were closely correlated with the process of metastasis from colon to lung. These altered metabolites indicated the disturbance of metabolism in metastatic tumors including glycolysis, TCA cycle, glutaminolysis, choline metabolism and serine biosynthesis. Our findings firstly identified the distinguishing metabolites in mouse colorectal cancer lung metastasis models, and indicated that the metabolite disturbance may be associated with the progression of lung metastasis from colon cancer. The altered metabolites may be potential biomarkers that provide a promising molecular approach for clinical diagnosis and mechanistic study of colorectal cancer with lung metastasis.
肺转移是结直肠癌患者 5 年生存率低的一个重要原因。了解结直肠癌肺转移的代谢特征对于开发分子诊断和治疗方法很重要。我们使用 1H 核磁共振（1H-NMR）对结直肠癌小鼠肺转移模型的肺组织样本进行代谢组学分析。在 BALB/c 小鼠静脉注射海洋结肠癌细胞系 CT-26 后，在不同时间点收集小鼠的肺组织。使用基于 1H-NMR 的代谢组学分析方法研究了肺组织的特征代谢物，这是一种用于鉴定生物标志物的高度敏感且非破坏性方法。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 图谱数据以寻找潜在的生物标志物。所有 3 种分析均在正常组和转移组之间实现了极好的分离。共鉴定出 42 种代谢物，其中约 12 种与从结肠转移到肺的过程密切相关。这些改变的代谢物表明转移瘤中的代谢紊乱，包括糖酵解、三羧酸循环、谷氨酰胺分解、胆碱代谢和丝氨酸生物合成。我们的研究结果首次鉴定了小鼠结直肠癌肺转移模型中的特征代谢物，并表明代谢物紊乱可能与结肠癌肺转移的进展有关。改变的代谢物可能是潜在的生物标志物，为结直肠癌伴肺转移的临床诊断和机制研究提供了有前途的分子方法。
