Qiao Li-Yan, Li Han-Bing, Zhang Yue, Shen Di, Liu Peng, Che Yi-Qun
Department of Stomatology, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, People's Republic of China.
Department of Clinical Laboratory, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People's Republic of China.
Pharmgenomics Pers Med. 2021 May 25;14:591-599. doi: 10.2147/PGPM.S310816. eCollection 2021.
Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin's lymphoma and of which the prognosis of activated B-cell-like (ABC) subtype is poor. Although R-CHOP significantly improves the survival of patients with DLBCL, 20% to 40% of patients were resistant to R-CHOP therapy. Thus, screening for candidate therapeutic targets for R-CHOP resistant patients is urgent. The previous researches have shown that CD24 is related to the development, invasion, and metastasis of cancer. Our project aims to clarify the relationship between CD24 and ABC-DLBCL.
The expression of CD24 mRNA in 118 ABC-DLBCL cases treated with R-CHOP was detected by RNAscope, and the relationship between CD24 expression and R-CHOP treatment response was analyzed. The correlation between CD24 expression and treatment efficiency was further analyzed by data downloaded from the Gene Expression Omnibus (GEO) database. The association between CD24 expression and immune response was conducted using Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT) methodology and Gene Ontology (GO) biological process (BP) analysis.
The positive expression rate of CD24 mRNA in ABC-DLBCL patients was 38.1% (45/118). Complete Response (CR) rate was significantly higher in patients with CD24 high expression than those with CD24 low expression (=0.039; 44.4% vs 26.0%). CR rate was significantly different between CD24 high and low expression groups in the analysis of GEO datasets (=0.003; 83.2% vs 58.0%). The CD24 high expression patients had significantly lower proportions of T cells and nonspecific immune cells in the CIBERSORT analysis. In addition, T-helper 2 cell differentiation and monocyte chemotaxis were repressed in CD24 high expression group in the GO BP analysis.
CD24 was correlated with better R-CHOP treatment response and tumor immunosuppression in ABC-DLBCL. CD24 may be a promising signal in treatment and prognosis evaluation in ABC-DLBCL patients.
弥漫性大B细胞淋巴瘤（DLBCL）是最常见的非霍奇金淋巴瘤，其中活化B细胞样（ABC）亚型的预后较差。尽管R-CHOP显著提高了DLBCL患者的生存率，但仍有20%至40%的患者对R-CHOP治疗耐药。因此，迫切需要为R-CHOP耐药患者筛选候选治疗靶点。先前的研究表明，CD24与癌症的发生、侵袭和转移有关。我们的项目旨在阐明CD24与ABC-DLBCL之间的关系。
采用RNAscope检测118例接受R-CHOP治疗的ABC-DLBCL病例中CD24 mRNA的表达，并分析CD24表达与R-CHOP治疗反应之间的关系。通过从基因表达综合数据库（GEO）下载的数据进一步分析CD24表达与治疗效果之间的相关性。使用通过估计RNA转录本相对子集进行细胞类型鉴定（CIBERSORT）方法和基因本体（GO）生物学过程（BP）分析来研究CD24表达与免疫反应之间的关联。
ABC-DLBCL患者中CD24 mRNA的阳性表达率为38.1%（45/118）。CD24高表达患者的完全缓解（CR）率显著高于CD24低表达患者（P = 0.039；44.4%对26.0%）。在GEO数据集分析中，CD24高表达组和低表达组之间的CR率有显著差异（P = 0.003；83.2%对58.0%）。在CIBERSORT分析中，CD24高表达患者的T细胞和非特异性免疫细胞比例显著较低。此外，在GO BP分析中，CD24高表达组的辅助性T细胞2分化和单核细胞趋化受到抑制。
CD24与ABC-DLBCL中更好的R-CHOP治疗反应和肿瘤免疫抑制相关。CD24可能是ABC-DLBCL患者治疗和预后评估中有前景的信号。
