Abstract
N-Acylethanolamine Acid Amidase (NAAA) is an N-terminal cysteine hydrolase and plays a vital physiological role in inflammatory response. However, the roles of NAAA 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 NAAA expression in prognosis and tumor immunity response. We would like to reveal the potential correlations between NAAA 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 NAAA displayed abnormal expression within most malignant tumors, and overexpression of NAAA was associated with the poor prognosis of tumor patients. Through gene set enrichment analysis (GSEA), we found that NAAA 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 NAAA 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 NAAA is co-expressed with genes encoding major histocompatibility complex (MHC), immune activation, immune suppression, chemokine, and chemokine receptors. Meanwhile, we demonstrate that NAAA expression was correlated with TMB in 4 cancers and with MSI in 10 cancers. Our study reveals that NAAA 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.
Highlights
As a worldwide threat to public health, malignant tumors bring endless suffering to patients and their families and add huge economic burden to society
For tumor tissues in the Cancer Genome Atlas (TCGA), we found N-Acylethanolamine Acid Amidase (NAAA) expression was the highest in prostate adenocarcinoma (PRAD) and lowest in uveal melanoma (UVM) (Figure 1B)
Results from databases revealed that NAAA was overexpressed in 10 of these cancers: breast invasive carcinoma (BRCA), lymphoid neoplasm, diffuse large B cell lymphoma (DLBC), glioblastoma multiforme (GBM), acute myeloid leukemia (LAML), ovarian cancer (OV), pancreatic adenocarcinoma (PAAD), pheochromocytoma and paraganglioma (PCPG), A
Summary
As a worldwide threat to public health, malignant tumors bring endless suffering to patients and their families and add huge economic burden to society. Tumor microenvironment may play a critical role in these potential mechanisms [5,6,7]. Tumor immunotherapy, which is different from conventional chemotherapeutics, has witnessed dramatic advances in cancer treatment, immune checkpoint blockade therapy [11, 12]. The clinical success of immune checkpoint inhibitors (ICIs), such as anti-programmed cell death protein-1 (PD-1) or its ligand (PD-L1) and anti-cytotoxic T lymphocyte-associated protein 4 (CTLA-4), have been approved the standard of care in many types of malignancies [13,14,15]. In addition to tumor cell-intrinsic factors, such as insufficient tumor antigenicity, disruption of interferon-g signal pathway, and downregulation surface MHC-I level [16, 17], the TME plays a major role in immunosuppression and affects clinical outcomes of cancer patients. There is an urgent need to search for new immune-related therapeutic targets in cancers
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