Organic and Biological Analytical Chemistry Group (OBiAChem), MolSys, University of Liège, 4000 Liège, Belgium.
GIGA Institute, Translational Gastroenterology and CHU de Liège, Hepato-Gastroenterology and Digestive Oncology, Quartier Hôpital, University of Liège, Avenue de l'Hôpital 13, B34-35, 4000 Liège, Belgium.
Int J Mol Sci. 2023 Jun 1;24(11):9614. doi: 10.3390/ijms24119614.
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.
结直肠癌（CRC）是全球第三大常见癌症，也是癌症相关死亡的第二大主要原因。目前基于内镜或粪便的诊断技术要么高度侵入性，要么缺乏足够的灵敏度。因此，需要一种侵入性更小、更敏感的筛查方法。因此，我们使用最先进的 GC×GC-LR/HR-TOFMS（二维气相色谱法与低/高分辨率飞行时间质谱联用）对代表三个不同组（腺癌、腺瘤和对照组）的 64 个人血清样本进行了研究。我们使用两种不同的专门针对脂质组学（脂肪酸）（25 μL 血清）和代谢组学（50 μL 血清）的特定样品制备方法来分析样本。应用有监督和无监督的方法进行深入的化学计量学筛选，并对两个数据集进行代谢途径分析。脂质组学研究表明，特定的多不饱和脂肪酸（ω-3）分子与 CRC 风险增加呈负相关，而一些多不饱和脂肪酸（ω-6）分析物呈正相关。代谢组学方法表明 CRC 中氨基酸（丙氨酸、谷氨酸、蛋氨酸、苏氨酸、酪氨酸和缬氨酸）和肌醇下调，而 3-羟基丁酸水平升高。这项独特的研究提供了与 CRC 相关的分子水平变化的全面见解，并允许使用相同的血清样本和单一仪器对两种不同的 CRC 筛查分析方法的效率进行比较。
