Background: Colorectal cancer (CRC) represents a third leading cause of cancer-related death worldwide. The reliable diagnostic biomarkers for detecting CRC at early stage is critical for decreasing the mortality. Method: A conjunctive lipidomic approach was employed to investigate the differences in plasma lipid profiles of CRC patients (n = 101) and healthy volunteers (n = 52). Based on UHPLC-Q-TOF MS and UHPLC-QQQ MS platforms, a total of 235 lipids were structurally detected. Multivariate data analysis was conducted including partial least squared discriminant analysis (PLS-DA), fold change performance and Mann-Whitney U test. Results: A total of 11 lipid species, including 1 Glycerophosphoethanolamine (PE), 3 ethanolamine plasmalogens (PlsEtn), 1 plasmanyl glycerophosphatidylethanolamine (PE-O), 3 fatty acids (FFA), 1 Fatty acid ester of hydroxyl fatty acid (FAHFA), and 2 Diacylglycerophosphates (PA) were identified to distinguish the CRC patients at early stage from healthy controls. In addition, these potential lipid biomarkers achieved an estimated AUC=0.981 in a validation set for univariate ROC analysis. Conclusion: By combining Q-TOF MS and QQQ MS analysis, the 11 lipids exhibited good performance in differentiating early-stage CRC and healthy control. This study also demonstrated that the lipidomics is a powerful tool in discovering new potential biomarkers for cancer diagnosis.

Elucidating the dysregulated metabolic pathways in cancer cells and their relevance to cisplatin resistance could yield new insights into cancer therapy. We previously reported that eight metabolites involved in the tricarboxylic acid (TCA) cycle and glutamine metabolism were associated with platinum-based chemotherapy efficacy in human lung cancer. Here, we investigated the metabolic differences upon cisplatin treatment in lung cancer in vitro and in vivo. A simple and partially validated standard addition method was applied for the quantification of five metabolites involved in the TCA cycle and glutamine metabolism using amide hydrophilic interaction liquid chromatography-tandem mass spectrometry (HILIC-MS/MS). The present study investigated the levels of these biomarkers in A549 cells and the cisplatin-resistant A549-DDP cells, as well as in the plasma before and after cisplatin treatment in A549 xenograft mice. Levels of five metabolites, including 2-hydroxyglutaric acid (2-HG), α-ketoglutarate (α-KG), succinate, glutamine, and glutamate, showed a decreasing trend in A549-DDP cells. In addition, 2-HG and glutamine were the most significantly altered metabolites in cisplatin-treated A549 xenograft mice. These data indicate that the TCA cycle and glutamine metabolism play important roles in cisplatin-based chemotherapy resistance in lung cancer. Our results provide a new angle for exploring the molecular mechanisms underlying cisplatin resistance.