Comprehensive multi-omics analysis identifies NUSAP1 as a potential prognostic and immunotherapeutic marker for lung adenocarcinoma.

While NUSAP1's association with various tumors is established, its predictive value for prognosis and immunotherapy in lung adenocarcinoma (LUAD) remains unconfirmed. We analyzed Nucleolar Spindle-Associated Protein 1 (NUSAP1) gene expression in TCGA and GTEx datasets and validated it in clinicopathological tissues using qRT-PCR and immunohistochemistry. Additionally, we investigated NUSAP1's relationship with patient prognosis across TCGA and five GEO cohorts. The IMvigor210 cohort was utilized to explore NUSAP1's association with immunotherapy efficacy. Furthermore, single-cell RNA-sequencing data was used to examine the correlation between NUSAP1 and immune cell infiltration. Finally, we analyzed the relationship between NUSAP1 and m6A methylation. NUSAP1 expression was significantly elevated in tumor tissues, correlating with poorer prognosis in LUAD patients. It exhibited a significant correlation with immune cell infiltration in the tumor microenvironment, predominantly expressed in Tprolif cells. LUAD patients with heightened NUSAP1 expression may derive greater benefit from anti-PD-L1 treatment. Additionally, NUSAP1 was tightly linked with m6A methylation. Enrichment analysis revealed its association with key biological functions, including lipid metabolism and cell cycle regulation. Our comprehensive analysis underscores NUSAP1's potential as a prognostic and immunotherapeutic biomarker for LUAD, warranting further investigation.