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

SIMPLE SUMMARY: The implications of extracellular nicotinamide phosphoribosyltransferase (eNAMPT) in colonic polyps remain uncertain. A 2-year prospective cohort study was conducted. Of 532 patients, 80 (15%) had prominent malignant potential (PMP) in colonic polyps, including villous adenomas, adenomas with high-grade dysplasia, and adenocarcinomas. Baseline associations were observed: colonic polyp pathology, total cholesterol, and neutrophil-to-lymphocyte ratio with eNAMPT levels, and age, polyp size, and eNAMPT levels with polyp pathology. Baseline eNAMPT levels were higher in patients harboring polyps with PMP than in patients without PMP, and baseline eNAMPT levels predicted PMP (cutoff: >4.238 ng/mL). Proportions of eNAMPT-positive glandular and stromal cells were higher in polyps with PMP than in polyps without PMP. eNAMPT levels decreased within 48 weeks postpolypectomy 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. 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. 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.