Abstract

Protein palmitoylation, a reversible post-translational lipid modification, has been implicated in regulating cancer cell signaling and progression; however, its role in prostate cancer (PCa) remains unclear. In this study, we comprehensively analyzed palmitoylation-related genes (PRGs) in PCa by integrating bulk transcriptomic, single-cell RNA sequencing, and spatial transcriptomic datasets. Unsupervised consensus clustering based on PRG expression identified two molecular subtypes with distinct prognoses, immune infiltration profiles, and pathway activities. Differential expression and weighted gene co-expression network analyses revealed five key feature genes, among which KIFC2 was highly expressed in tumor cells and correlated with poor clinical outcomes. The KIFC2 was predominantly enriched in high-grade adenocarcinoma regions. Functional experiments demonstrated that silencing KIFC2 significantly inhibited proliferation and promoted apoptosis in PC3 and DU145 prostate cancer cell lines. Additionally, high KIFC2 expression was associated with increased cell cycle progression and oncogenic signaling pathways, including KRAS and PI3K-AKT. Collectively, these results suggest that palmitoylation and KIFC2 play critical roles in PCa progression and may serve as promising biomarkers and therapeutic targets.