Wen Xiang-Mei, Xu Zi-Jun, Ni Hao-Xi, Liu Su-Wan, Jin Ye, Zhao Wei, Luo Shu-Yu, Fang Yuan-Yuan, Mao Zhen-Wei, Lin Jiang, Qian Jun
Laboratory Center, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu, China.
Zhenjiang Clinical Research Center of Hematology, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu, China.
Front Immunol. 2025 Jul 2;16:1569641. doi: 10.3389/fimmu.2025.1569641. eCollection 2025.
Depending on the cellular context and cancer type, FOXP1 functions as an oncogene or a tumor suppressor. However, the clinical role of FOXP1 in hematologic malignancies has not been studied comprehensively. This study systematically analyzed the association of FOXP1 expression with clinical outcomes, including prognosis and immunotherapeutic response, as well as biological functions across a range of hematological cancers. Our findings demonstrated that FOXP1 expression was dysregulated in several hematological malignancies and was associated with poor prognosis. FOXP1 was highly expressed in acute myeloid leukemia (AML). Methylation of the FOXP1 promoter was significantly reduced in patients with AML compared to the healthy control subjects and those with myelodysplastic syndromes. FOXP1 promoter methylation showed an inverse relationship with FOXP1 gene expression in AML. Moreover, FOXP1 expression was associated with the tumor infiltration of B cells, natural killer cells, and T cells, as well as the cytolytic score across various hematologic malignancies. Our data showed that FOXP1 expression was a promising biomarker for predicting responses to immunotherapy in AML patients. Functionally, the knockdown of FOXP1 demonstrated antileukemic effects, including reduced AML cell proliferation and cell cycle arrest in the G1-S phase. In conclusion, this study systematically investigated the role of FOXP1 across a spectrum of hematological malignancies and demonstrated that FOXP1 was a promising prognostic biomarker and a potential therapeutic target in AML and other hematological malignancies.
根据细胞环境和癌症类型，FOXP1可作为癌基因或肿瘤抑制基因发挥作用。然而，FOXP1在血液系统恶性肿瘤中的临床作用尚未得到全面研究。本研究系统分析了FOXP1表达与临床结局（包括预后和免疫治疗反应）以及一系列血液系统癌症的生物学功能之间的关联。我们的研究结果表明，FOXP1表达在几种血液系统恶性肿瘤中失调，并与不良预后相关。FOXP1在急性髓系白血病（AML）中高表达。与健康对照受试者和骨髓增生异常综合征患者相比，AML患者中FOXP1启动子的甲基化显著降低。在AML中，FOXP1启动子甲基化与FOXP1基因表达呈负相关。此外，FOXP1表达与B细胞、自然杀伤细胞和T细胞的肿瘤浸润以及各种血液系统恶性肿瘤的细胞溶解评分相关。我们的数据表明，FOXP1表达是预测AML患者免疫治疗反应的一个有前景的生物标志物。在功能上，敲低FOXP1显示出抗白血病作用，包括降低AML细胞增殖和使细胞周期停滞在G1-S期。总之，本研究系统地研究了FOXP1在一系列血液系统恶性肿瘤中的作用，并证明FOXP1是AML和其他血液系统恶性肿瘤中有前景的预后生物标志物和潜在的治疗靶点。
