Extracellular Nicotinamide Phosphoribosyltransferase as a Surrogate Marker of Prominent Malignant Potential in Colonic Polyps: A 2-Year Prospective Study

Abstract

Background/aims: The implications of extracellular nicotinamide phosphoribosyltransferase (eNAMPT), a cancer metabokine, in colonic polyps remain uncertain. Methods: A 2-year prospective cohort study of patients who underwent colonoscopy was conducted. Biochemical parameters and serum eNAMPT levels were analyzed at baseline and every 24 weeks postpolypectomy. NAMPT-associated single-nucleotide polymorphisms (SNPs), including rs61330082, rs2302559, rs10953502, and rs23058539, were assayed. Results: Of 532 patients, 80 (15%) had prominent malignant potential (PMP) in colonic polyps, including villous adenomas (n = 18, 3.3%), adenomas with high-grade dysplasia (n = 33, 6.2%), and adenocarcinomas (n = 29, 5.5%). Baseline associations were as follows: colonic polyp pathology (p < 0.001), total cholesterol (p = 0.019), and neutrophil-to-lymphocyte ratio (p = 0.023) with eNAMPT levels; and age (p < 0.001), polyp size (p < 0.001), and eNAMPT levels (p < 0.001) with polyp pathology. Higher baseline eNAMPT levels were noted in patients harboring polyps with PMP than in patients without PMP (p < 0.001), and baseline eNAMPT levels significantly predicted PMP (cutoff: >4.238 ng/mL, p < 0.001). Proportions of eNAMPT-positive glandular and stromal cells were higher in polyps with PMP than in polyps without PMP (64.55 ± 11.94 vs. 14.82 ± 11.45%, p = 0.025). eNAMPT levels decreased within 48 weeks postpolypectomy (p = 0.01) and remained stable afterward regardless of PMP until 96 weeks postpolypectomy. However, those with PMP had a higher degree of eNAMPT decline within 24 weeks (p = 0.046). All investigated SNPs were in linkage disequilibrium with each other but were not associated with eNAMPT levels. Conclusion: With a link to inflammation and lipid metabolism, along with its decreasing trend after polypectomy, serum eNAMPT may serve as a surrogate marker of PMP in colonic polyps. In situ probing of the NAMPT-associated pathway holds promise in attenuating PMP, as much of the eNAMPT likely originates from colonic polyps.