Department of Epidemiology and Biostatistics, School of Public Health, Harbin Medical University, Harbin 150086, China.
Department of Colorectal Surgery, The Affiliated Tumor Hospital of Harbin Medical University, Harbin 150086, China.
Clin Chim Acta. 2018 Dec;487:357-362. doi: 10.1016/j.cca.2018.10.010. Epub 2018 Oct 5.
Many studies have demonstrated that right-sided colon cancer (RCC) has a higher mortality rate and worse prognosis than left-sided colon cancer (LCC). However, the underlying biological mechanism that can account for these differences is unclear.
In this study, plasma metabolic profiles in 147 LCC patients and 105 RCC patients were systematically analyzed by the ultra high performance liquid chromatography quadruple time-of-flight mass spectrometry (UHPLC-QTOF/MS) platform in conjunction with univariate and multivariate statistical analysis.
Metabolic signatures revealed considerable differences between patients with RCC and LCC, and clear separations were observed between the two groups in partial least-squares discriminant analysis score plots. In total, six metabolites were identified as potential metabolite markers for tumor location in RCC compared with LCC, including upregulated trimethylamine N-oxide and indoxyl sulfate, and downregulated anserine, L-targinine, gamma-glutamyl-gamma-aminobutyraldehyde and pyridoxal 5'-phosphate. These differences highlight that significant alternations occur in the pathways of methane metabolism, arginine and proline metabolism, histidine metabolism, beta-alanine metabolism and vitamin B6 metabolism in RCC compared with LCC.
Identified biomarkers and metabolic pathways may facilate our understanding of the different mortality rates and prognoses between RCC and LCC.
许多研究表明,右半结肠癌(RCC)的死亡率和预后比左半结肠癌(LCC)更高。然而,导致这些差异的潜在生物学机制尚不清楚。
本研究通过超高效液相色谱四级杆飞行时间质谱联用仪(UHPLC-QTOF/MS)平台,结合单变量和多变量统计分析,对 147 例 LCC 患者和 105 例 RCC 患者的血浆代谢谱进行了系统分析。
代谢特征揭示了 RCC 患者和 LCC 患者之间存在显著差异,两组在偏最小二乘判别分析得分图中明显分离。共有 6 种代谢物被鉴定为 RCC 肿瘤位置的潜在代谢标志物,与 LCC 相比,包括上调的三甲胺 N-氧化物和吲哚硫酸,以及下调的肌氨酸、L-精氨酸、γ-谷氨酰-γ-氨基丁酸和吡哆醛 5'-磷酸。这些差异表明,与 LCC 相比,RCC 中甲烷代谢、精氨酸和脯氨酸代谢、组氨酸代谢、β-丙氨酸代谢和维生素 B6 代谢途径发生了显著变化。
鉴定出的生物标志物和代谢途径可能有助于我们理解 RCC 和 LCC 之间不同的死亡率和预后。