Global serum metabolomic and lipidomic analyses reveal lipid perturbations and potential biomarkers of the colorectal cancer by adenoma-carcinoma sequence
Yifan Zhu, Hailin Zhou, Hongwei Chen, Jiahao Zhang, Yunxiao Liang, Shanyi Yang, Xuancheng Wang, Guanghui CHEN, Qisong Zhang
Abstract
The colorectal adenoma-carcinoma (CA-CRC) sequence is a recognized concept for the development of colorectal cancer (CRC), and investigation of potential biomarkers targeting this pathway may aid in the early detection and prevention of CRC. In this study, metabolomic analysis of normal (NR), colorectal adenoma (CA), and CRC groups using ultra-performance liquid chromatography-tandem high-resolution mass spectrometry (UHPLCHRMS) technique preliminarily disclosed a crucial role of dysregulation of lipid metabolism in CRC development. This was further illustrated by using lipidomic analysis which found that phosphatidylcholine (PC) and triacylglycerol (TAG) metabolism was markedly disturbed with CRC progression. Based on that, the receiver operating characteristic (ROC) analysis of differential lipids from lipidomics identified 50 candidate biomarkers with good diagnostic ability for the CA-CRC sequence. Among these, the panel of progressively differential lipids including O-(4,8-dimethylnonyl)carnitine, LPC 19:0, TAG 58:1, and PC 38:7 showed satisfactory diagnostic performance in the CA-CRC sequence, with the area under the ROC curve (AUC) of 0.878, 0.817, and 0.805, respectively. In summary, our work demonstrated the key role of perturbation of PC and TAG metabolism in the CA-CRC sequence combining serum metabolomics and lipidomics, and firstly established a lipid biomarker-panel with good performance, providing helpful references and novel prevention strategies for CRC.