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Background: Understanding the metabolic changes in colorectal cancer (CRC) and exploring potential diagnostic biomarkers is crucial for elucidating its pathogenesis and reducing mortality. Cancer cells are typically derived from cancer tissues and can be easily obtained and cultured. Systematic studies on CRC cells at different stages are still lacking. Additionally, there is a need to validate our previous findings from human serum. Methods: Ultrahigh-performance liquid chromatography tandem high-resolution mass spectrometry (UHPLC-HRMS)-based metabolomics and lipidomics were employed to comprehensively measure metabolites and lipids in CRC cells at four different stages and serum samples from normal control (NR) and CRC subjects. Univariate and multivariate statistical analyses were applied to select the differential metabolites and lipids between groups. Biomarkers with good diagnostic efficacy for CRC that existed in both cells and serum were screened by the receiver operating characteristic curve (ROC) analysis. Furthermore, potential biomarkers were validated using metabolite standards. Results: Metabolite and lipid profiles differed significantly among CRC cells at stages A, B, C, and D. Dysregulation of glycerophospholipid (GPL), fatty acid (FA), and amino acid (AA) metabolism played a crucial role in the CRC progression, particularly GPL metabolism dominated by phosphatidylcholine (PC). A total of 46 differential metabolites and 29 differential lipids common to the four stages of CRC cells were discovered. Eight metabolites showed the same trends in CRC cells and serum from CRC patients compared to the control groups. Among them, palmitoylcarnitine and sphingosine could serve as potential biomarkers with the values of area under the curve (AUC) more than 0.80 in the serum and cells. Their panel exhibited excellent performance in discriminating CRC cells at different stages from normal cells (AUC = 1.00). Conclusions: To our knowledge, this is the first research to attempt to validate the results of metabolism studies of serum from CRC patients using cell models. The metabolic disorders of PC, FA, and AA were closely related to the tumorigenesis of CRC, with PC being the more critical factor. The panel composed of palmitoylcarnitine and sphingosine may act as a potential biomarker for the diagnosis of CRC, aiding in its prevention. [ABSTRACT FROM AUTHOR]

Colorectal advanced adenoma (CAA) is a key precancerous lesion of colorectal cancer (CRC), and early diagnosis can lessen CRC morbidity and mortality. Although abnormal lipid metabolism is associated with the development of CRC, there are no studies on the biomarkers and mechanism of lipid metabolism linked to CAA carcinogenesis. Hence, we performed a lipidomics study of serum samples from 46 CAA, and 50 CRC patients by the ultra high-performance liquid chromatography tandem high resolution mass spectrometry (UHPLC-HRMS) in both electrospray ionization (ESI) modes. Differential lipids were selected by univariate and multivariate statistics analysis, and their diagnostic performance was evaluated using a receiver operating characteristic curve (ROC) analysis. Combining P < 0.05 and variable importance in projection (VIP) > 1, 59 differential lipids were obtained totally. Ten of them showed good discriminant ability for CAA and CRC (AUC > 0.900). Especially, the lipid panel consisting of PC 44:5, PC 35:6e, and SM d40:3 showed the highest selection frequency and outperformed (AUC = 0.952). Additionally, phosphatidylcholine (PC) and sphingomyelin (SM) were the main differential and high-performance lipids. In short, this is the first study to explore the biomarkers and mechanism for CAA-CRC sequence with large-scale serum lipidomics. The findings should provide valuable reference and new clues for the development of diagnostic and therapeutic strategies of CRC. [Display omitted] • Obvious differences in serum lipid profiles between CAA and CRC. • Discovery of biomarkers of CAA carcinogenesis by non-targeted lipidomics. • Disorders of PC and SM metabolism are associated with CAA cancerization. [ABSTRACT FROM AUTHOR]