NKAIN1 predicts poor prognosis and associated with drug resistance and immune infiltration in prostate adenocarcinoma

Abstract

Na, K-ATPase interaction 1 (NKAIN1) is a transmembrane protein that can interact with Na, K-ATPase β1 subunit. NKAIN1 has prognostic value in several cancers, but its biomarker and carcinogenic roles in the development of prostate adenocarcinoma (PRAD) remain underexplored. The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) database were used to analyze the expression and prognostic significance of NKAIN1 in PRAD. The Genomics of Drug Sensitivity in Cancer (GDSC) database and The Cancer Therapeutics Response Portal (CTRP) database were used to analyze drug resistance. Single-cell RNA sequencing was employed to define cell clusters. GO, KEGG, and GSEA enrichment analyses were performed to predict the function of NKAIN1-related factors. Finally, CCK8, Colony formation assay, transwell experiments, and subcutaneous tumor formation in nude mice were conducted to validate the role of NKAIN1 in PRAD development. NKAIN1 was significantly upregulated in PRAD, correlating with advanced TNM stages, poor survival, and may be involved in drug resistance. High NKAIN1 expression was associated with altered immune infiltration. Additionally, NKAIN-related genes were enriched in Wnt signaling, metabolism, and immune-related pathways. Knockdown of NKAIN1 suppressed PRAD cell proliferation, migration, invasion, and immune evasion in vitro and tumor growth in vivo. NKAIN1 serves as a prognostic, drug resistance, and immune infiltration marker. Moreover, NKAIN1 promotes PRAD progression and suggests it acts as a potential therapeutic target. This research has been retrospectively registered in the Ethics Committee institutional of the First Affiliated Hospital of Soochow University with the number of 2025–733.