{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:14:53Z","timestamp":1791918893123,"version":"4.3.4"},"reference-count":63,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,1,6]],"date-time":"2022-01-06T00:00:00Z","timestamp":1641427200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>N-Acylethanolamine Acid Amidase (<jats:italic>NAAA<\/jats:italic>) is an N-terminal cysteine hydrolase and plays a vital physiological role in inflammatory response. However, the roles of <jats:italic>NAAA<\/jats:italic> in tumor immunity are still unclear. By using a series of bioinformatics approaches, we study combined data from different databases, including the Cancer Genome Atlas, the Cancer Cell Line Encyclopedia, Genotype Tissue-Expression, cBioPortal, Human Protein Atlas, TIMER, and ImmuCellAI to investigate the role of <jats:italic>NAAA<\/jats:italic> expression in prognosis and tumor immunity response. We would like to reveal the potential correlations between <jats:italic>NAAA<\/jats:italic> expression and gene alterations, tumor mutational burden (TMB), microsatellite instability (MSI), DNA methylation, tumor microenvironment (TME), immune infiltration levels, and various immune-related genes across different cancers. The results show that <jats:italic>NAAA<\/jats:italic> displayed abnormal expression within most malignant tumors, and overexpression of <jats:italic>NAAA<\/jats:italic> was associated with the poor prognosis of tumor patients. Through gene set enrichment analysis (GSEA), we found that <jats:italic>NAAA<\/jats:italic> was significantly associated with cell cycle and immune regulation-related signaling pathways, such as in innate immune system, adaptive immune system, neutrophil degranulation, and Toll-like receptor signaling pathways (TLRs). Further, the expression of <jats:italic>NAAA<\/jats:italic> was also confirmed to be correlated with tumor microenvironment and diverse infiltration of immune cells, especially tumor-associated macrophage (TAM). In addition to this, we found that <jats:italic>NAAA<\/jats:italic> is co-expressed with genes encoding major histocompatibility complex (MHC), immune activation, immune suppression, chemokine, and chemokine receptors. Meanwhile, we demonstrate that <jats:italic>NAAA<\/jats:italic> expression was correlated with TMB in 4 cancers and with MSI in 10 cancers. Our study reveals that <jats:italic>NAAA<\/jats:italic> plays an important role in tumorigenesis and cancer immunity, which may be used to function as a prognostic biomarker and potential target for cancer immunotherapy.<\/jats:p>","DOI":"10.3389\/fimmu.2021.812713","type":"journal-article","created":{"date-parts":[[2022,1,6]],"date-time":"2022-01-06T13:34:43Z","timestamp":1641476083000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Insights Into the Prognostic Value and Immunological Role of NAAA in 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