Li Tengfei, Li Xun, Kang Pengcheng, Zhao Jinmin
The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
Department of Orthopedics, Loudi Central Hospital, Ward 32, Loudi, China.
Transl Oncol. 2025 Mar;53:102283. doi: 10.1016/j.tranon.2025.102283. Epub 2025 Jan 20.
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.
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.
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.
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.
肉瘤（SARC）是一组起源于间充质组织的恶性肿瘤，其特点是在传统治疗下预后较差。CX3CR1是一种参与免疫细胞迁移的趋化因子受体，已成为肉瘤中的关键因子。磷酸化和泛素化等翻译后修饰（PTM）对CX3CR1起着关键调节作用，影响癌症进展、免疫反应和治疗耐药性。
本研究调查CX3CR1在肉瘤中的表达、生物学功能和预后价值。利用来自癌症基因组图谱（TCGA）的数据，我们分析了CX3CR1基因表达、甲基化模式、CRISPR筛选结果和免疫浸润指标。功能实验包括敲除和过表达模型、CCK-8检测和流式细胞术以评估细胞凋亡。
CX3CR1在肉瘤组织中的表达显著升高，与总生存期、疾病特异性生存期和无进展生存期呈正相关。甲基化分析确定了与CX3CR1表达相关的CpG位点，可区分肿瘤组织和相邻组织。CRISPR筛选突出了CX3CR1在肿瘤生长中的重要作用，而免疫浸润分析强调了其对肿瘤微环境的影响。发现PTM可稳定CX3CR1，增强其在关键信号通路中的活性。CX3CR1的过表达增强了炎症和凋亡反应，而敲低在体外显示出保护作用。
CX3CR1有望成为肉瘤的预后生物标志物和治疗靶点。针对CX3CR1的PTM可能会推动个性化治疗并改善肉瘤患者的预后。
