NNMT involving with gastric adenocarcinoma immune infiltration by driving amino acids metabolism

Abstract

Objectives Gastric cancer is a malignant tumor with high incidence rate and high mortality. Gastric adenocarcinoma (STAD) is the main pathological type of gastric cancer. Nicotinamide N-methyltransferase (NNMT) is a methylation enzyme that primarily participates in the metabolism of nicotinamide (NAM) in the body, which is highly expressed in many solid tumor tissues and is associated with cancer progression and tumor microenvironment. NNMT is a hot spotlight in the development of STAD. Methods Bioinformatics data Basing on the Cancer Genome Atlas (TCGA) was withdrawn and analyzed to explore the character of NNMT in STAD. Tissues from clinical patient specimens were collected and conducted Western blot and immunohistochemistry to explore the localization and expression of NNMT in cancer tissues and adjacent normal tissues of STAD patients. The profiles of amino acids in cancer tissues and adjacent normal tissues of STAD patients were compared. The relationship between of NNMT and genes to differential amino acids was further mapped. Results Bioinformatics analysis from the TCGA database revealed that NNMT is highly expressed in cancer tissues of STAD patients and influences tumor immune infiltration. The outcome from clinical specimen confirmed that both the NNMT mRNA and protein expression was significantly increased in cancer tissues of STAD patients compared to adjacent normal tissues. 28 differential amino acids, including alanine, leucine, aspartic acid, and glutamic acid etc. 10 differential amino acid metabolic enzymes, including GPX3, GAMT, AMD1, and ODC1 etc. were associated with NNMT. Clinical specimens confirmed a negative correlation between GPX3, GAMT, and AMD1 mRNA expression and NNMT. Conclusion NNMT is highly expressed in STAD tissues and may drive amino acid metabolites changes by their enzymes, thus influence STAD immune infiltration and tumorigenesis.