Metabolomics and transcriptomics identify pathway differences between visceral and subcutaneous adipose tissue in colorectal cancer patients: the ColoCare study
Metabolomics and transcriptomics identify pathway differences between visceral and subcutaneous adipose tissue in colorectal cancer patients: the ColoCare study
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DOI：
10.3945/ajcn.114.103804
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发表时间：
2015-08-01
影响因子：
7.1
通讯作者：
Ulrich, Cornelia M.
中科院分区：
文献类型：
--
作者：
Liesenfeld, David B.;Grapov, Dmitry;Ulrich, Cornelia M.
背景：内脏脂肪组织(VAT)和皮下脂肪组织(SAT)之间的代谢和转录差异，特别是在肥胖的情况下，可能在结直肠癌的发生中发挥作用。目的：利用质谱学、代谢组学和基因表达谱研究结直肠癌(CRC)患者脂肪组织(VAT和SAT)的生化差异。比较VAT、SAT和血清代谢物的组成。设计：收集ColoCare队列中59例肿瘤分期为I~IV期的结直肠癌患者的术前血和术中VAT、SAT配对样本。采用气相色谱-飞行时间-质谱仪和高效液相四极杆飞行时间-质谱仪分别测定了1065种脂肪组织代谢物(333种鉴定化合物)和1810种血清代谢物(467种鉴定化合物)。结果：与SAT组相比，VAT组大鼠的炎性脂代谢指标、游离花生四烯酸、磷脂酶(PLA2G10)和前列腺素合成相关酶(PTGD/PTGS2S)均显著升高。VAT组血浆纤溶酶原浓度低于SAT组，这与VAT中酯-脂合成限速酶Far！基因表达降低有关。血清鞘磷脂浓度与SAT脂肪甘油三酯呈负相关(P=0.0001)。Logistic回归分析发现患者脂肪组织中的脂类与结直肠癌的肿瘤分期有关。结论：作为首批研究之一，我们综合评估了配对的人类VAT和SAT在代谢、脂类和转录水平上的差异及其与结直肠癌肿瘤分期的关系。我们确定了增值税中的炎症标志物，这支持了先前关于内脏肥胖和癌症的作用的证据。这项试验在Clinicaltrials.gov上注册为NCT02328677。
Background: Metabolic and transcriptomic differences between visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) compartments, particularly in the context of obesity, may play a role in colorectal carcinogenesis. We investigated the differential functions of their metabolic compositions.Objectives: Biochemical differences between adipose tissues (VAT compared with SAT) in patients with colorectal carcinoma (CRC) were investigated by using mass spectrometry metabolomics and gene expression profiling. Metabolite compositions were compared between VAT, SAT, and serum metabolites. The relation between patients' tumor stage and metabolic profiles was assessed.Design: Presurgery blood and paired VAT and SAT samples during tumor surgery were obtained from 59 CRC patients (tumor stages I-IV) of the ColoCare cohort. Gas chromatography time-of-flight mass spectrometry and liquid chromatography quadrupole time-of-flight mass spectrometry were used to measure 1065 metabolites in adipose tissue (333 identified compounds) and 1810 metabolites in serum (467 identified compounds). Adipose tissue gene expression was measured by using Illumina's HumanHT-12 Expression BeadChips.Results: Compared with SAT, VAT displayed elevated markers of inflammatory lipid metabolism, free arachidonic acid, phospholipases (PLA2G10), and prostaglandin synthesis related enzymes (PTGD/PTGS2S). Plasmalogen concentrations were lower in VAT than in SAT, which was supported by lower gene expression of FAR!, the rate-limiting enzyme for ether-lipid synthesis in VAT. Serum sphingomyelin concentrations were inversely correlated (P = 0.0001) with SAT adipose triglycerides. Logistic regression identified lipids in patients' adipose tissues, which were associated with CRC tumor stage.Conclusions: As one of the first studies, we comprehensively assessed differences in metabolic, lipidomic, and transcriptomic profiles between paired human VAT and SAT and their association with CRC tumor stage. We identified markers of inflammation in VAT, which supports prior evidence regarding the role of visceral adiposity and cancer. This trial was registered at clinicaltrials.gov as NCT02328677.