Metabolomic profiling identifies biomarkers and metabolic impacts of surgery for colorectal cancer

Abstract

BackgroundColorectal cancer (CRC) is one of the most common malignant tumors with recurrence and metastasis after surgical resection. This study aimed to identify the physiological changes after surgery and explore metabolites and metabolic pathways with potential prognostic value for CRC.MethodsAn ultra-high-performance liquid chromatography Q-exactive mass spectrometry was used to profile serum metabolites from 67 CRC patients and 50 healthy volunteers. Principal component analysis (PCA) and orthogonal projections to latent structures-discriminant analysis were used to distinguish the internal characteristics of data in different groups. Multivariate statistics were compiled to screen the significant metabolites and metabolic pathways.ResultA total of 180 metabolites were detected. Under the conditions of variable importance in projection >1 and p-value <0.05, 46 differentially expressed metabolites were screened for further pathway enrichment analysis. Based on the Kyoto Encyclopedia of Genes and Genomes database and Small Molecule Pathway Database, three metabolic pathways—arginine and proline metabolism, ascorbate and aldarate metabolism, and phenylalanine metabolism—were significantly altered after surgical resection and identified as associated with the removal of CRC. Notably, gamma-linolenic acid was upregulated in the CRC preoperative patients compared with those in healthy volunteers but returned to healthy levels after surgery.ConclusionThrough serum-based metabolomics, our study demonstrated the differential metabolic characteristics in CRC patients after surgery compared with those before surgery. Our results suggested that metabonomic analysis may be a powerful method for exploring physiological alterations in CRC patients after surgery as well as a useful tool for identifying candidate biomarkers and monitoring disease recurrence.

Circulating metabolites as potential biomarkers for the early detection and prognosis surveillance of gastrointestinal cancers

“…Here a few studies that focused on the metabolic changes by surgery in gastric and colorectal cancer. The most influenced metabolic pathways were amino acid and lipid metabolism, and ascorbate and aldarate metabolism after surgical resection in GC and CRC patients (Jung et al, 2014;Lee et al, 2020;Vignoli et al, 2021;Zhuang et al, 2022). In this study, we detected the plasma metabolites after surgical treatment and performed a comparison with those before surgery from the identical subject.…”

“…In addition, relevant research has demonstrated that tumor resection surgery events can distinctly change the metabolic characteristics in multiple cancer types. For example, curative surgery significantly changes the level of γ -linolenic acid in CRC and alanine, arginine, and hypoxanthine in GC (Jung et al, 2014;Zhuang et al, 2022).…”

Circulating Metabolites as Potential Biomarkers for the Early Detection and Prognosis Surveillance of Gastric and Colon Cancers

“…Brie y, 5 mL of peripheral blood was collected and centrifuged at 4°C (3,800 rpm, 10 min), and the supernatant was harvested for metabolite extraction. Samples (50 uL) were mixed with 700 uL MTBE buffer containing 0.45 µg/mL of gibberellic acid A3, 1 µg/mL of 13 C sorbitol, and 0.45 µg/mL of PC(17:0/14:1) as internal standards [16]. The addition of 350 uL methanol/water (v/v, 1:3) was used for phase separation.…”

“…In addition, relevant research has demonstrated that tumor resection surgery events can distinctly change the metabolic characteristics in multiple cancer types. For example, curative surgery signi cantly changes the level of γ -linolenic acid in CRC and alanine, arginine, and hypoxanthine in GC [13,14].…”