Plasma metabolomic profiling distinguishes right-sided from left-sided colon cancer

Plasma metabolomic profiling distinguishes right-sided from left-sided colon cancer
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血浆代谢组学分析可区分右侧和左侧结肠癌

DOI:
10.1016/j.cca.2018.10.010
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发表时间:
2018-12-01
影响因子:
5
通讯作者:
Li, Kang
Li, Kang
中科院分区:
医学3区
文献类型:
--
作者:
Deng, Kui;Han, Peng;Li, Kang

文献摘要

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背景:大量研究表明,右侧结肠癌(RCC)比左侧结肠癌(LCC)死亡率高,预后差。方法:采用超高效液相四重飞行时间质谱仪(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。结果:RCC和LCC患者的代谢特征存在显著差异,偏最小二乘判别分析计分图显示两组患者的代谢特征有明显差异。与LCC相比,共有6种代谢物被鉴定为潜在的肿瘤定位代谢物标志物,包括上调的三甲胺N-氧化物和吲哚硫酸盐,下调的氨丝氨酸、L-油氨酸、γ-谷氨酰-γ-氨基丁醛和5‘-磷酸吡哆醛。这些差异凸显了肾细胞癌与肝细胞癌相比,其甲烷代谢、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。结论:识别的生物标志物和代谢途径有助于了解肾细胞癌和肝细胞癌死亡率和预后的差异。
Background 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.Methods: 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.Results: 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.Conclusions: Identified biomarkers and metabolic pathways may facilate our understanding of the different mortality rates and prognoses between RCC and LCC.