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

Tsung-Hsing Chen; Hung-Chih Hsu; Jeng-Fu You; Cheng-Chou Lai; Yung-Kuan Tsou; Chia-Lin Hsu; Cathy S J Fann; Rong-Nan Chien; Ming-Ling Chang

doi:10.3390/cancers15061702

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

Cancers (Basel). 2023 Mar 10;15(6):1702. doi: 10.3390/cancers15061702.

Authors

Tsung-Hsing Chen^{1

2}, Hung-Chih Hsu^{2

3}, Jeng-Fu You^{2

4}, Cheng-Chou Lai^{2

4}, Yung-Kuan Tsou^{1

2}, Chia-Lin Hsu⁵, Cathy S J Fann⁵, Rong-Nan Chien^{1

2}, Ming-Ling Chang^{1

2}

Affiliations

¹ Division of Hepatology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan.
² Department of Medicine, College of Medicine, Chang Gung University, Taoyuan 33305, Taiwan.
³ Division of Hematology-Oncology, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan.
⁴ Colorectal Section, Department of Surgery, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan.
⁵ Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan.

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.

Keywords: PBEF; advanced colonic polyp; colonoscopy; visfatin.

Grants and funding

This study was supported by grants from the Chang Gung Medical Research Program (CMRPG3I0413, CMRPG3L1191, CMRPG3M0211, and CMRPG1K0111-3) and the National Science Council, Taiwan (MOST 110-2629-B-182-001-, 110-2314-B-182-044-, 111-2629-B-182-001-, and 111-2314-B-182A-156-). The funders had no role in the study design, data collection, or analysis.