Immunometabolic Biomarkers in Colorectal Cancer: An Exploratory Diagnostic Evaluation of PBEF/NAMPT, Chemerin, and Osteopontin

Abstract

Immunometabolic dysregulation plays a pivotal role in colorectal cancer (CRC) development and progression. Among the molecules linking inflammation, metabolism, and tumorigenesis, pre-B-cell colony-enhancing factor/nicotinamide phosphoribosyltransferase (PBEF/NAMPT), chemerin, and osteopontin (OPN) have emerged as promising circulating biomarkers. This single-center study evaluated their diagnostic performance in patients with colorectal cancer and compared their utility with established tumor markers. Serum concentrations of PBEF/NAMPT, chemerin, and OPN were determined using a magnetic bead-based multiplex immunoassay (Luminex technology), whereas carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) were measured by chemiluminescent microparticle immunoassay (CMIA). The study included 76 patients with colorectal cancer and 38 healthy, colonoscopy-negative controls. Differences between groups were assessed using the Mann–Whitney U, Kruskal–Wallis and post hoc tests, and diagnostic performance was evaluated by receiver operating characteristic (ROC) curve analysis. Serum concentrations of PBEF/NAMPT and OPN were significantly higher in patients with CRC than in healthy controls, whereas chemerin did not differ significantly between groups. Among the investigated immunometabolic biomarkers, OPN demonstrated the highest diagnostic accuracy (AUC = 0.747), followed by PBEF/NAMPT (AUC = 0.624), whereas chemerin showed no significant diagnostic value (AUC = 0.559). Combining immunometabolic biomarkers with CEA yielded numerically higher AUC values than CEA alone, with the OPN + CEA panel reaching the highest diagnostic accuracy (AUC = 0.910), followed by the PBEF/NAMPT + CEA combination (AUC = 0.875); however, these increases did not reach statistical significance when formally compared with CEA alone. Among the evaluated immunometabolic biomarkers, OPN demonstrated the greatest diagnostic potential for colorectal cancer, and its combination with CEA warrants further investigation, although these findings should be considered exploratory given the limited sample size and the absence of external validation. Larger, multicenter studies using clinically relevant comparator groups are needed to establish the clinical utility of such multimarker strategies for the non-invasive diagnosis of CRC.