结直肠癌(CRC)是第三大最常见的诊断癌症,也是癌症相关死亡的第二大原因。当前的基于内窥镜或基于粪便的诊断技术是高度侵入性的或缺乏足够的灵敏度。因此,需要更少侵入性和更敏感的筛查方法。我们,因此,对代表三个不同组的64个人血清样本进行了研究(腺癌,腺瘤,和对照)使用尖端的GC×GC-LR/HR-TOFMS(全面的二维气相色谱与低/高分辨率飞行时间质谱联用)。我们用两种不同的专门定制的样品制备方法分析了脂质组学(脂肪酸)(25μL血清)和代谢组学(50μL血清)的样品。采用有监督和无监督方法的深入化学计量学筛查以及代谢途径分析被应用于这两个数据集。一项脂质组学研究表明,特定的PUFA(ω-3)分子与CRC的几率增加呈负相关。而一些PUFA(ω-6)分析物显示出正相关。代谢组学方法揭示了氨基酸(丙氨酸,谷氨酸,蛋氨酸,苏氨酸,酪氨酸,和缬氨酸)和肌醇在CRC中,而3-羟基丁酸水平升高。这项独特的研究提供了对与CRC相关的分子水平变化的全面了解,并允许比较使用相同血清样品和单一仪器进行CRC筛查的两种不同分析方法的效率。
Colorectal cancer (CRC) ranks as the third most frequently diagnosed cancer and the second leading cause of cancer-related deaths. The current endoscopic-based or stool-based diagnostic techniques are either highly invasive or lack sufficient sensitivity. Thus, there is a need for less invasive and more sensitive screening approaches. We, therefore, conducted a
study on 64 human serum samples representing three different groups (adenocarcinoma, adenoma, and control) using cutting-edge GC×GC-LR/HR-TOFMS (comprehensive two-dimensional gas chromatography coupled with low/high-resolution time-of-flight mass spectrometry). We analyzed samples with two different specifically tailored sample preparation approaches for lipidomics (fatty acids) (25 μL serum) and metabolomics (50 μL serum). In-depth chemometric screening with supervised and unsupervised approaches and metabolic pathway analysis were applied to both datasets. A lipidomics
study revealed that specific PUFA (ω-3) molecules are inversely associated with increased odds of CRC, while some PUFA (ω-6) analytes show a positive correlation. The metabolomics approach revealed downregulation of amino acids (alanine, glutamate, methionine, threonine, tyrosine, and valine) and myo-inositol in CRC, while 3-hydroxybutyrate levels were increased. This unique
study provides comprehensive insight into molecular-level changes associated with CRC and allows for a comparison of the efficiency of two different analytical approaches for CRC screening using same serum samples and single instrumentation.