Abstract
BACKGROUND: Sarcomas (SARC) are a diverse group of malignant tumors originating from mesenchymal tissues, characterized by poor prognosis under conventional therapies. CX3CR1, a chemokine receptor involved in immune cell migration, has emerged as a key player in SARC. Post-translational modifications (PTMs) such as phosphorylation and ubiquitination critically modulate CX3CR1, influencing cancer progression, immune responses, and treatment resistance. METHODS: This study investigates CX3CR1 expression, its biological functions, and prognostic value in SARC. Using data from The Cancer Genome Atlas (TCGA), we analyzed CX3CR1 gene expression, methylation patterns, CRISPR screening results, and immune infiltration metrics. Functional experiments included knockout and overexpression models, CCK-8 assays and flow cytometry to assess apoptosis. RESULTS: CX3CR1 expression was significantly elevated in SARC tissues and positively correlated with overall survival, disease-specific survival, and progression-free intervals. Methylation analysis identified CpG sites associated with CX3CR1 expression, differentiating tumor and adjacent tissues. CRISPR screening highlighted CX3CR1's essential role in tumor growth, while immune infiltration analysis underscored its impact on the tumor microenvironment. PTMs were found to stabilize CX3CR1, enhancing its activity in key signaling pathways. Overexpression of CX3CR1 amplified inflammatory and apoptotic responses, while knockdown showed protective effects in vitro. CONCLUSIONS: CX3CR1 serves as a promising prognostic biomarker and therapeutic target in sarcoma. Targeting CX3CR1's PTMs could advance personalized treatments and improve outcomes for sarcoma patients.