Integrated Elementomics-Genomics-Metabolomics Analysis Reveals Plasma Biomarker Networks and Diagnostic Potential for...

Background: Gastric cancer remains a leading cause of cancer-related deaths worldwide. Although significant progress has been made in clinical diagnosis and treatment, the molecular mechanisms underlying gastric cancer have not yet been fully elucidated. To address this, this study employs a multi-omics approach to systematically analyze the molecular characteristics of gastric cancer. Methods: This case-control study enrolled 218 GC patients and 218 healthy controls, and adopted a multi-omics strategy combining inductively coupled plasma mass spectrometry (ICP-MS), element-related genome-wide association study (eGWAS), and untargeted metabolomics to explore the element-gene-metabolite regulatory axis in GC. Results: A total of nine plasma differential elements associated with gastric cancer were identified, with a combined diagnostic accuracy of 0.918. Specifically, elements such as Fe, Co, and Li showed significant correlations with 63 genes involved in key signaling pathways, including MAPK, SMAD, and Wnt. Genome-wide association studies (GWAS) revealed that gastric cancer-related genes were significantly enriched in cancer-associated pathways and signaling cascades such as Rap1. Metabolomic analysis further demonstrated that 20 elements in the gastric cancer cohort correlated with 94 metabolites, predominantly enriched in pyrimidine and glutathione metabolism pathways. Conclusions: These nine plasma differential elements showed high combined diagnostic efficacy and were associated with genes and metabolites enriched in cancer-related signaling, metabolic reprogramming, and DNA damage response pathways. Together, these findings suggest potential multi-level associations among plasma elemental alterations, genetic variation, and metabolic dysregulation in GC, providing candidate circulating biomarkers and mechanistic clues for future investigation.