The Role of Omentin in Gastrointestinal Cancer: Diagnostic, Prognostic, and Therapeutic Perspectives

Background/Objectives: Gastrointestinal (GI) cancer, including colorectal, gastric, pan-creatic, hepatic, and esophageal malignancies, remains a major global health burden, with limited predictive biomarkers and targeted therapies. Omentin, also known as intelectin-1, is a secreted adipokine with anti-inflammatory, insulin-sensitizing, and immune-modulatory functions, primarily expressed in visceral adipose tissue. While omentin has been associated with favorable metabolic outcomes, its role in cancer pathogenesis appears context-dependent and remains poorly understood. This review investigates the biological functions, expression patterns, and clinical relevance of omentin across GI malignancies. Methods: A comprehensive review of the literature was conducted to evaluate the role of omentin in gastrointestinal cancers. Studies investigating omentin’s expression in tumor tissues, blood, and adipose tissue, its prognostic signifi-cance, and its therapeutic potential were analyzed. Preclinical and clinical studies ex-ploring the effects of omentin analogues or omentin-enhancing agents were also re-viewed. Results: Omentin exhibits anti-proliferative, anti-inflammatory, and an-ti-angiogenic effects within the tumor microenvironment in several GI malignancies. High intratumoral omentin expression correlates with improved prognosis in colorectal, gastric, and hepatic cancers, whereas elevated circulating levels, particularly in colorectal and pancreatic cancers, have been paradoxically associated with increased cancer risk and poor outcomes. Moreover, omentin-1 inhibits key oncogenic pathways including PI3K/Akt and NF-κB, modulates immune cell infiltration, and suppresses cancer stem cell activity. However, its different mechanism of action in systemic versus local level remains a major unresolved issue. Conclusions: Omentin demonstrates significant diagnostic, prognostic, and therapeutic potential across gastrointestinal cancers, with evidence supporting its tumor-suppressive and immunomodulatory functions. However, its con-text-dependent behavior -especially the disparity between circulating and tu-mor-localized expression- necessitates further translational studies which could validate its clinical utility and therapeutic potential across different tumor types.