Remodeling of Oncogene-Related Molecular Networks Following Bariatric Surgery: a Multi-Omics Study

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Abstract
Obesity is a well-established risk factor for multiple cancers, and Metabolic Bariatric Surgery (MBS) has been associated with reduced cancer incidence and mortality. However, the molecular mechanisms underlying this risk reduction remain incompletely understood. Many recent transcriptomic, proteomic, and metabolomic studies have enabled system-wide molecular profiling following MBS. We performed a systematic analysis of publicly available MBS-related omics datasets, including transcriptomic ( n = 22), proteomic ( n = 6), and metabolomic studies ( n = 5), with pre- and post-operative comparisons. Comparative molecular analyses across all omics datasets were performed using Ingenuity Pathway Analysis (IPA). Sustained suppression of key oncogenic pathways, including Molecular Mechanisms of Cancer, Role of Tissue Factor in Cancer, and metastasis-associated signaling, was observed in tissue transcriptomic datasets (adipose, skeletal muscle, and gastrointestinal tract). In contrast, transcriptomic datasets predominantly showed immune remodeling, characterized by activation of innate immune pathways. Key molecular markers, including CCL2 , EGFL6 , and S100A8, were identified as consistently regulated across multiple datasets. Proteomic analyses revealed early postoperative suppression of inflammatory and acute-phase proteins, progressive downregulation of complement and coagulation cascades, and sustained upregulation of endocrine regulators such as sex hormone-binding globulin and extracellular matrix–stabilizing factors. Metabolomic profiling demonstrated significant alterations in amino acid, bile acid, and lipid metabolism following MBS. These molecular changes collectively reflect a shift toward a less inflammatory, hormonally balanced, and metabolically favorable systemic environment. These findings highlight the impact of MBS in inhibiting cancer-promoting biological processes and identify candidate molecular biomarkers for future translational and oncologic research.

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