Background: Glucosamine 6-phosphate N-acetyltransferase 1 (GNPNAT1) serves as a critical rate-limiting enzyme within the hexosamine biosynthetic pathway (HBP). However, its expression patterns, clinical significance in various cancers, and role in modulating the tumor immune microenvironment are not well understood. Methods: This study analyzed the differential expression patterns of GNPNAT1 and its potential association with patient prognosis using pan-cancer datasets. Using a multi-omics approach and multiple databases, we examined the correlations between GNPNAT1 expression and tumor stemness, mutational profiles, RNA modifications, the tumor immune microenvironment, and drug sensitivity. Additionally, we conducted enrichment analyses and in vitro functional experiments for cervical cancer (CC) to preliminarily elucidate the signaling pathways and biological processes that GNPNAT1 may regulate. Results: GNPNAT1 exhibits aberrant expression in various tumor types, and its expression levels hold substantial prognostic implications for some cancer patients. In certain tumors, GNPNAT1 expression is associated with tumor mutational profiles, RNA modifications, and drug sensitivity. Furthermore, the study found that GNPNAT1 expression levels correlate with key molecules, including immune checkpoint genes, chemokines, and immunostimulatory factors. Enrichment analyses in CC suggests that GNPNAT1 may be involved in cell adhesion and immune-related pathways. Knockdown of GNPNAT1 was shown by in vitro functional assays, significantly attenuated CC cell proliferation and migration. Conclusion: GNPNAT1 may serve as a promising prognostic biomarker for certain tumors, such as CC. Its association with immune regulation and treatment resistance highlights its potential as a new target for immunotherapy interventions.
Liu et al. (2026) studied this question.