Potential role of glucosamine-phosphate N-acetyltransferase 1 in the development of lung adenocarcinoma

Abstract

Glucosamine-phosphate N-acetyltransferase 1 (GNPNAT1) is a key enzyme associated with glucose metabolism and uridine diphosphate-N-acetylglucosamine biosynthesis. Abnormal GNPNAT1 expression might be associated with carcinogenesis. We analyzed multiple lung adenocarcinoma (LUAD) gene expression databases and verified GNPNAT1 higher expression in LUAD tumor tissues than in normal tissues. Moreover, we analyzed the survival relationship between LUAD patients’ clinical status and GNPNAT1 expression, and found higher GNPNAT1 expression in LUAD patients with unfavorable prognosis. We built GNPNAT1 gene co-expression networks and further annotated the co-expressed genes’ Gene Ontology (GO) terms, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and various associated regulatory factors. These co-expression genes’ functional networks mainly participate in chromosome segregation, RNA metabolic process, and RNA transport. We analyzed GNPNAT1 genetic alterations and co-occurrence networks, and the functional networks of these genes showed that GNPNAT1 participates in multiple steps of cell cycle transition and in the development of some cancers. We assessed the correlation between GNPNAT1 expression and cancer immune infiltrates and showed that GNPNAT1 expression is correlated with several immune cells, chemokines, and immunomodulators in LUAD. We found that GNPNAT1 correlates with LUAD development and prognosis, laying a foundation for further research, especially in immunotherapy.

A novel metabolic-immune related signature predicts prognosis and immunotherapy response in lung adenocarcinoma

“…NPAS2 was demonstrated to be a potential prognostic biomarker in colorectal and breast cancers [ 25 , 26 ], and facilitated cell survival in hepatocellular carcinoma through trans-activation of CDC25A [ 27 ]. Several studies had collectively indicated that GNPNAT1 was closely related to poor prognosis in lung adenocarcinoma [ 28 , 29 ], and MELTF can be considered as a prognostic marker in lung adenocarcinoma and gastric cancer [ 30 , 31 ]. In summary, many studies have shown that five genes, DKK1, CCL20, NPAS2, GNPNAT1 and MELTF, are engaged in the pathogenesis and progression of multiple tumors.…”

GNPNAT1 Predicts Poor Prognosis and Cancer Development in Non-Small Cell Lung Cancer

“…The results of GNPNAT1 gene coexpression network analysis indicated that GNPNAT1 might participate in cell cycle transition, cancer development and immune infiltration in LUAD. 11 The other two studies also reported a correlation between GNPNAT1 and immune infiltration, indicating the potential function of GNPNAT1 in immunomodulation and immunotherapy. 9,21 In this study, we analysed GNPNAT1 expression in NSCLC.…”

“…Several recent studies also reached consistent conclusions about GNPNAT1 in LUAD. [9][10][11][12] However, few studies have reported the function of GNPNAT1 in NSCLC or LUSC. In addition, GNPNAT1 represents the key molecule facilitating the enhanced therapeutic effects of Abraxane on NSCLC.…”

“…8 In recent years, several studies have been published sequentially and indicated that GNPNAT1 upregulation predicts poor prognosis in LUAD patients. [9][10][11][12] Zhao et al found that Abraxane was a promising drug to treat NSCLC, and the application of Abraxane resulted in significant downregulation of GNPNAT1 in lung cancer cells. 13 GNPNAT1 might play an important role in NSCLC biological processes and represent an underlying biomarker for prognosis.…”

O-GlcNAcylation links oncogenic signals and cancer epigenetics

“…For example, PGM3 has been reported to be overexpressed in prostate carcinoma [ 135 ]. GNPNAT1 is overexpressed in lung adenocarcinoma patients, which correlates with unfavorable prognosis [ 136 ]. GNPNAT1 is increased in prostate cancer compared with normal tissue [ 137 ] but GNPNAT1 level decreases as tumors become castration-resistant, indicating stage-specific roles of HBP during prostate cancer progression [ 137 ].…”