Plasma metabolites associated with colorectal cancer stage: Findings from an international consortium
Plasma metabolites associated with colorectal cancer stage: Findings from an international consortium
复制标题
DOI：
10.1002/ijc.32666
复制
发表时间：
2019-10-10
影响因子：
6.4
通讯作者：
Kok, Dieuwertje E.
中科院分区：
文献类型：
--
作者：
Geijsen, Anne J. M. R.;van Roekel, Eline H.;Kok, Dieuwertje E.
结直肠癌是全球癌症相关死亡的第二大常见原因，诊断时疾病阶段的预后存在显著差异。我们研究了与疾病阶段相关的循环代谢物，以提高对与结直肠癌进展相关的代谢途径的理解。我们研究了来自正在进行的队列研究的744名I-IV期结直肠癌患者中130种代谢物的血浆浓度。使用Biocrates AbsoluteIDQ（TM）p180试剂盒，用液相色谱-质谱法分析诊断时收集的血浆样品。我们使用多项和多变量逻辑回归模型评估代谢物浓度和分期之间的关联。对分析进行了潜在混杂因素调整，并使用错误发现率（FDR）校正进行了多重检验。分别有23%、28%、39%和10%的患者出现I-IV期疾病。与I期患者相比，III期患者的鞘磷脂C26：0浓度较低（p（FDR）< 0.05）。与I期患者相比，IV期患者的鞘磷脂C18：0和磷脂酰胆碱（二酰基）C32：0浓度在统计学上显著较高，而瓜氨酸、组氨酸、磷脂酰胆碱（二酰基）C34：4、磷脂酰胆碱（酰基-烷基）C40：1和溶血磷脂酰胆碱（酰基）C16：0和C17：0浓度较低（p（FDR）< 0.05）。我们的研究结果表明，涉及瓜氨酸和组氨酸的代谢途径，以前与结直肠癌的发展有关，也可能与结直肠癌的进展有关。
Colorectal cancer is the second most common cause of cancer-related death globally, with marked differences in prognosis by disease stage at diagnosis. We studied circulating metabolites in relation to disease stage to improve the understanding of metabolic pathways related to colorectal cancer progression. We investigated plasma concentrations of 130 metabolites among 744 Stages I-IV colorectal cancer patients from ongoing cohort studies. Plasma samples, collected at diagnosis, were analyzed with liquid chromatography-mass spectrometry using the Biocrates AbsoluteIDQ (TM) p180 kit. We assessed associations between metabolite concentrations and stage using multinomial and multivariable logistic regression models. Analyses were adjusted for potential confounders as well as multiple testing using false discovery rate (FDR) correction. Patients presented with 23, 28, 39 and 10% of Stages I-IV disease, respectively. Concentrations of sphingomyelin C26:0 were lower in Stage III patients compared to Stage I patients (p(FDR) < 0.05). Concentrations of sphingomyelin C18:0 and phosphatidylcholine (diacyl) C32:0 were statistically significantly higher, while citrulline, histidine, phosphatidylcholine (diacyl) C34:4, phosphatidylcholine (acyl-alkyl) C40:1 and lysophosphatidylcholines (acyl) C16:0 and C17:0 concentrations were lower in Stage IV compared to Stage I patients (p(FDR) < 0.05). Our results suggest that metabolic pathways involving among others citrulline and histidine, implicated previously in colorectal cancer development, may also be linked to colorectal cancer progression.