Tumor stromal nicotinamide N-methyltransferase overexpression as a prognostic biomarker for poor clinical outcome in early-stage colorectal cancer Journal Article

   

Authors:	Ogawa, M.; Tanaka, A.; Namba, K.; Shia, J.; Wang, J. Y.; Roehrl, M. H. A.
Article Title:	Tumor stromal nicotinamide N-methyltransferase overexpression as a prognostic biomarker for poor clinical outcome in early-stage colorectal cancer
Abstract:	In a quest for prognostic biomarkers in early-stage colorectal cancer, we investigated NNMT (nicotinamide N-methyltransferase) in large cohorts of patients. Immunohistochemical examination of 679 patients illustrates that NNMT protein is predominantly expressed in the cancer stroma at varying levels, and about 20% of cancer tissues overexpress NNMT when compared to levels observed in normal colorectal mucosa. Clinical correlation analyses of 572 patients with early-stage cancers reveal that NNMT protein overexpression is significantly associated with shorter overall and disease-free survival, but no such correlation is found in late-stage colorectal cancer. Analyses of TCGA and CPTAC colorectal cancer cohorts show that NNMT mRNA expression is positively correlated with protein levels, is significantly higher in CIMP-high or MSI subtypes than in CIMP-low or MSS subtypes, and is positively correlated with its paralog INMT but not with its interaction partners such as PNMT, ADK, APP, ATF6, BMF, BRD4, CDC37, or CRYZ. In early-stage cancers, NNMT expression is higher in BRAF-mutated than in BRAF wild type tumors but is not affected by KRAS or PIK3CA mutation status. As a cancer stromal protein with important roles in metabolism and cancer epigenetics, NNMT is emerging as a promising biomarker for risk stratification of early-stage cancers. © 2022. The Author(s).
Journal Title:	Scientific Reports
Volume:	12
ISSN:	2045-2322
Publisher:	Nature Publishing Group
Date Published:	2022-02-17
Start Page:	2767
Language:	English
DOI:	10.1038/s41598-022-06772-w
PUBMED:	35177765
PROVIDER:	scopus
PMCID:	PMC8854702
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85124776030&doi=10.1038%2fs41598-022-06772-w&partnerID=40&md5=0c0aa4b377e1f1a00908652cd2827bf0
Notes:	Article -- Export Date: 1 March 2022 -- Source: Scopus

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