背景:分化簇24(CD24)是一种高度糖基化的糖基磷脂酰肌醇(GPI)锚定的表面蛋白,在各种肿瘤细胞中表达,作为“不要吃我”的信号分子在肿瘤免疫。本研究旨在探讨CD24在泛癌症中的潜在特征。
方法:使用TIMER分析22种免疫细胞与CD24表达之间的相关性。R包“估计”用于预测泛癌症中免疫和基质细胞的比例。进行Spearman相关性分析以评估CD24表达与免疫检查点之间的关系。趋化因子,失配修复,肿瘤突变负荷和微卫星不稳定性,进行qPCR和蛋白质印迹以评估CD24在肝细胞癌(LIHC)中的表达水平。此外,对LIHC中CD24的生物学评估进行了功能丧失.
结果:CD24表达与骨髓细胞呈正相关,包括中性粒细胞和骨髓来源的抑制细胞,在各种肿瘤中,如BLCA,HNSC-HPV,HNSC,KICH,KIRC,KIRP,TGCT,THCA,THYM,和UCEC。相比之下,抗肿瘤NK细胞和NKT细胞与BRCA-Her2、ESCA、HNSC-HPV,KIRC,THCA,和THYM。CD24与ImmuneScore相关性最高的前3位肿瘤为TGCT,THCA,SKCM。功能富集分析显示CD24表达与各种免疫相关途径呈负相关。免疫检查点和趋化因子也与CESC中的CD24呈负相关,CHOL,COAD,ESCA,READ,TGCT,和THCA。此外,CD24在大多数肿瘤中过度表达,在BRCA中CD24高表达,LIHC,CESC与不良预后相关。TIDE数据库显示CD24高表达的肿瘤,特别是黑色素瘤,对PD1/PD-L1免疫疗法的反应较低。最后,CD24敲低导致LIHC中增殖受损和细胞周期进展。
结论:CD24参与免疫浸润的调节,影响患者预后,并作为潜在的肿瘤标志物。
BACKGROUND: Cluster of differentiation 24 (
CD24) is a highly glycosylated glycosylphosphatidylinositol (GPI)-anchored surface protein, expressed in various tumor cells, as a \"don\'t eat me\" signaling molecule in tumor immune. This study aimed to investigate the potential features of
CD24 in pan-cancer.
METHODS: The correlations between 22 immune cells and CD24 expression were using TIMER analysis. R package \"ESTIMATE\" was used to predict the proportion of immune and stromal cells in pan-cancer. Spearman\'s correlation analysis was performed to evaluate the relationships between CD24 expression and immune checkpoints, chemokines, mismatch repair, tumor mutation burden and microsatellite instability, and qPCR and western blot were conducted to assess CD24 expression levels in liver hepatocellular carcinoma (LIHC). In addition, loss of function was performed for the biological evaluation of
CD24 in LIHC.
RESULTS: CD24 expression was positively correlated with myeloid cells, including neutrophils and myeloid-derived suppressor cells, in various tumors, such as BLCA, HNSC-HPV, HNSC, KICH, KIRC, KIRP, TGCT, THCA, THYM, and UCEC. In contrast, anti-tumor NK cells and NKT cells showed a negative association with CD24 expression in BRCA-Her2, ESCA, HNSC-HPV, KIRC, THCA, and THYM. The top three tumors with the highest correlation between CD24 and ImmuneScore were TGCT, THCA, and SKCM. Functional enrichment analysis revealed CD24 expression was negatively associated with various immune-related pathways. Immune checkpoints and chemokines also exhibited inverse correlations with CD24 in CESC, CHOL, COAD, ESCA, READ, TGCT, and THCA. Additionally,
CD24 was overexpressed in most tumors, with high
CD24 expression in BRCA, LIHC, and CESC correlating with poor prognosis. The TIDE database indicated tumors with high CD24 expression, particularly melanoma, were less responsive to PD1/PD-L1 immunotherapy. Finally,
CD24 knockdown resulted in impaired proliferation and cell cycle progression in LIHC.
CONCLUSIONS: CD24 participates in regulation of immune infiltration, influences patient prognosis and serves as a potential tumor marker.