Insights Into the Prognostic Value and Immunological Role of NAAA in Pan-Cancer

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.

Systematic pan-cancer analysis of the potential tumor diagnosis and prognosis biomarker P4HA3

“…We analyzed the protein expression level of P4HA3 using The Human Protein Atlas (HPA) database (https://www.proteinatlas.org). Many researchers have used this database to analyze the expression levels of target genes, such as Xiong et al, Zhou et al, Liu et al, and Xu et al used this database to study the expression levels of PIMREG, NAAA, CD2, and TUBA1C respectively, which tentatively proved their analysis results (Chen et al, 2021;Huang et al, 2021;Zhu et al, 2021;Hu et al, 2022).…”

Integrated analysis identifies oxidative stress-related lncRNAs associated with progression and prognosis in colorectal cancer

“…We further downloaded the reference list of MSI scores from the cBioPortal database ( https://www.cbioportal.org/ ) (Additional file 3 ) [ 66 ]. Samples with MSI scores greater than 10 were classified as the positive group, and those with MSI scores not greater than 10 were classified as the negative group.…”

Large-scale imputation models for multi-ancestry proteome-wide association analysis

“…NAAA encoded a lysosomal enzyme, playing an important role in inflammatory response 116 . NAAA has dysregulated expression patterns, which were correlated with tumor mutational burden and microsatellite instability in multiple cancers 117 . In summary, the application of our PWAS models to various complex traits and diseases suggests their consistent and reliable performance.…”