GNPNAT1 作为与肺腺癌免疫浸润相关的预后生物标志物，并促进癌细胞的增殖和侵袭

Lung cancer persists as the foremost cause of cancer-related mortality worldwide, with lung adenocarcinoma (LUAD) representing the predominant histological subtype. Although GNPNAT1 has been implicated as a prognostic indicator in breast and prostate malignancies, its functional significance and mechanistic role in LUAD remain to be elucidated.

We performed comprehensive bioinformatic analyses to compare GNPNAT1 expression levels and prognostic impact in LUAD versus normal pulmonary tissues. Functional enrichment and single-cell transcriptomic analyses were employed to infer GNPNAT1-associated biological pathways. Immune cell infiltration was quantified using established deconvolution algorithms to assess correlations with GNPNAT1 expression. In vitro assays-including Transwell migration/invasion, colony formation, and flow cytometric evaluation of apoptosis and cell-cycle distribution-were conducted following GNPNAT1 knockdown. Western blotting was utilized to measure alterations in cyclins, CDKs, and MAPK/ERK pathway proteins.

GNPNAT1 was significantly upregulated in LUAD specimens compared with non-neoplastic lung tissue (P < 0.001), and elevated expression portended reduced overall survival. Enrichment analyses highlighted GNPNAT1's involvement in cell proliferation and cell-cycle regulation. Correlation studies revealed that GNPNAT1 expression positively associated with Th2 cells, total T helper cells, and γδ T cells, while inversely correlating with Th17 cells, B lymphocytes, and CD8⁺ T cells. Functional suppression of GNPNAT1 markedly impaired LUAD cell proliferation, migration, and invasion in vitro (P < 0.01), induced apoptosis, and provoked G2/M cell-cycle arrest. Furthermore, GNPNAT1 silencing resulted in decreased levels of Cyclin B1, Cyclin D1, CDK1 (P < 0.01), and phosphorylated ERK.

GNPNAT1 is overexpressed in lung adenocarcinoma and serves as an adverse prognostic biomarker. Its modulation of immune cell infiltration and engagement of the ERK/MAPK signaling cascade underscores its potential as both a prognostic indicator and therapeutic target in LUAD.