Clinical performance and utility of a NNMT-based urine test for bladder cancer

Pozzi, Valentina; Ruscio, Giulia Di; Campagna, Roberto; Seta, Riccardo; Fulvi, Paola; Vici, Alexia; Milanese, Giulio; Brandoni, Gabriele; Galosi, Andrea Benedetto; Montironi, Rodolfo; Cecati, Monia; Emanuelli, Monica

doi:10.5301/ijbm.5000311

Cited by 30 publications

(40 citation statements)

References 39 publications

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“…High expression of NNMT has been reported in multiple cancer types . Several studies have shown that the elevated NNMT level in cancer can be used for the early diagnosis and noninvasive diagnosis of some malignant tumors . Interestingly, NNMT has been considered as a novel and sensitive serum biomarker for CRC detection, outperforming the clinical significance of carcinoembryonic antigen (CEA) .…”

Section: Introductionmentioning

confidence: 99%

“…[7][8][9][10][11][12] Several studies have shown that the elevated NNMT level in cancer can be used for the early diagnosis and noninvasive diagnosis of some malignant tumors. [13][14][15] Interestingly, NNMT has been considered as a novel and sensitive serum biomarker for CRC detection, outperforming the clinical significance of carcinoembryonic antigen (CEA). 12 However, it was recently reported that NNMT was expressed in stroma and served as a major metabolic regulator of ovarian cancer-associated fibroblasts (CAF).…”

Section: Introductionmentioning

confidence: 99%

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High stromal nicotinamide N‐methyltransferase (NNMT) indicates poor prognosis in colorectal cancer

Song

Miao

et al. 2020

Cancer Medicine

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Purpose Nicotinamide n‐methyltransferase (NNMT) has good biochemical activity and epigenetic regulation, and has been reported as a major metabolic regulator of cancer. The goal of this study was to investigate the significance of stromal NNMT expression in colorectal cancer (CRC). Patients and methods Stromal expression of NNMT in primary CRC, metastasis CRC, and their non‐cancerous tissues from 1088 CRC patients was examined by immunohistochemistry. The associations between stromal NNMT expression and survival outcomes in 967 patients with stage I‐III CRC were further evaluated with Kaplan‐Meier curve and Cox model analyses. Results NNMT expression was mainly sourced from stromal compartments and also elevated in CRC. Patients with high stromal NNMT (IHC‐score ≥ 106) have a worse survival than those patients with low stromal NNMT. In multiple Cox analyses, high expression of stromal NNMT remained as an independent risk factor in CRC for disease‐free survival with a hazard ratio (HR) of 1.415 (95% confidence interval [CI], 1.015‐1.972) and disease‐specific survival with a HR of 5.004 (95% CI, 2.301‐10.883). In addition, high stromal NNMT expression in CRC also indicates the poor survival outcomes in patients with early stage CRC (stage I and II) and in patients who undergo chemotherapy. Conclusion NNMT is mainly located in CRC stromal compartment. High stromal NNMT expression predicts an unfavorable postoperative prognosis.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

High stromal nicotinamide N‐methyltransferase (NNMT) indicates poor prognosis in colorectal cancer

Song

Miao

et al. 2020

Cancer Medicine

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“…These results are in agreement with what reported by other studies, which explored NNMT expression in different solid tumours. Indeed, enzyme upregulation was described in a wide variety of neoplasms, including papillary thyroid carcinoma, stomach, colorectal and pancreatic cancer, ccRCC, OSCC, BC, NSCLC and lastly in melanoma …”

Section: Discussionmentioning

confidence: 99%

“…Enzyme overexpression was reported in numerous neoplasms, including clear cell renal cell carcinoma (ccRCC), oral squamous cell carcinoma (OSCC), non‐small cell lung cancer (NSCLC), bladder cancer (BC) and recently cutaneous and oral malignant melanoma …”

Section: Introductionmentioning

confidence: 99%

“…In this work, the attention was focused on nicotinamide Nmethyltransferase (NNMT), a human cytosolic enzyme that catalyzes the N-methylation of nicotinamide, pyridines and other structural analogues. 10,11 Enzyme overexpression was reported in numerous neoplasms, including clear cell renal cell carcinoma (ccRCC), 12,13 oral squamous cell carcinoma (OSCC), [14][15][16] non-small cell lung cancer (NSCLC), 17 bladder cancer (BC) 18,19 and recently cutaneous and oral malignant melanoma. 20,21 Further analyses also explored the relationship between clinico-pathological parameters and NNMT tumour expression, in order to evaluate the effectiveness of the enzyme as a potential prognostic marker.…”

Section: Introductionmentioning

confidence: 99%

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Nicotinamide N‐methyltransferase in nonmelanoma skin cancers

Pompei

Salvolini

Rubini

et al. 2019

Eur J Clin Investigation

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Background Squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) represent the most common forms of nonmelanoma skin cancers (NMSCs). Although successful treatment of these neoplasms is based on surgical excision, an increasing number of BCCs relapses and many SCCs display high rates of recurrence and metastasis. Nicotinamide N‐methyltransferase (NNMT) is a cytosolic enzyme, which was found to be upregulated in different solid tumours. However, there are no data regarding enzyme expression in NMSCs. The aim of this study was therefore to evaluate the potential involvement of NNMT in BCCs and SCCs. Materials and methods Immunohistochemical analyses were carried out on 40 BCC cases and 39 SCC cases, to evaluate enzyme expression in tumour and surrounding healthy margins. Moreover, the relationship between NNMT intratumour levels and clinico‐pathological parameters were explored. Results Nicotinamide N‐methyltransferase was found to be overexpressed in BCCs compared with control tissues, while a significant enzyme downregulation was detected in SCCs with respect to corresponding healthy margins. In addition, NNMT levels were negatively related to aggressiveness of both BCCs (distinguishing between infiltrative and nodular tumours) and SCCs (considering head and neck forms and tumours of the extremities and trunk). Conclusions These evidences seem to demonstrate that the different NNMT dysregulation detected in BCC and SCC may be the result of important biological traits distinctively characterizing these two forms within NMSCs. In addition, enzyme levels seem to be inversely correlated with tumour aggressiveness, thus suggesting the potential suitability of the enzyme as a prognostic biomarker for both neoplasms.

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Elevated N‐methyltransferase expression induced by hepatic stellate cells contributes to the metastasis of hepatocellular carcinoma via regulation of the CD44v3 isoform

Shang

Zhang

et al. 2019

Molecular Oncology

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The cross‐talk between hepatic stellate cells (HSCs) and hepatic carcinoma cells contributes to hepatocellular carcinoma (HCC) progression, but the underlying mechanism is largely unknown. We report here that activated HSCs induce upregulation of nicotinamide N‐methyltransferase (NNMT), which is known to regulate multiple metabolic pathways in hepatoma cells of the liver. High levels of NNMT in HCC tissues were positively correlated with vascular invasion, increased serum HBV‐DNA levels, and distant metastasis. In addition, functional assays showed that NNMT promoted HCC cell invasion and metastasis by altering the histone H3 methylation on 27 methylation pattern and transcriptionally activating cluster of differentiation 44 (CD44). NNMT‐mediated N6‐methyladenosine modification of CD44 mRNA resulted in the formation of a CD44v3 splice variant, while its product 1‐methyl‐nicotinamide stabilized CD44 protein by preventing ubiquitin‐mediated degradation. Finally, NNMT was also shown to be a target of statins that inhibited metastasis of hepatoma cells. Taken together, our study shows for the first time that the NNMT/CD44v3 axis regulates HCC metastasis and presents NNMT as a promising prognostic biomarker and therapeutic target for HCC.

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Clinical performance and utility of a NNMT-based urine test for bladder cancer

Abstract: Our data indicate that NNMT is a promising biomarker that could be used to support the early and noninvasive diagnosis of BC.

Cited by 30 publications

References 39 publications

High stromal nicotinamide N‐methyltransferase (NNMT) indicates poor prognosis in colorectal cancer

High stromal nicotinamide N‐methyltransferase (NNMT) indicates poor prognosis in colorectal cancer

Nicotinamide N‐methyltransferase in nonmelanoma skin cancers

Elevated N‐methyltransferase expression induced by hepatic stellate cells contributes to the metastasis of hepatocellular carcinoma via regulation of the CD44v3 isoform

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