CD45^(+)CD326^(+)双阳性细胞的特征及其在膀胱癌预后预测中的作用

Characteristics of CD45^(+)CD326^(+)double⁃positive cells and their role in the prognostic prediction of bladder cancer

目的探讨CD45^(+)CD326^(+)双阳性细胞(double positive cells,DPCs)对膀胱癌预后的影响,并构建膀胱癌DPCs相关基因评分系统,探究不同DPCs评分膀胱癌患者肿瘤微环境的特征。方法采用单细胞测序技术分析DPCs的分子特征,质谱流式技术分析DPCs高比例组和低比例组患者的肿瘤微环境异质性。基于TCGA‐BLCA队列,根据DPCs的特征基因构建评分系统,并在GSE13507队列及GSE32894队列中进行验证。结果膀胱癌患者中DPCs高比例组患者的预后较低比例组患者的预后差(P=0.0158),且高、低比例组患者的肿瘤微环境存在异质性,高比例组患者较低比例患者的免疫细胞和肿瘤细胞有更高的免疫检查点、共抑制因子和共激活因子的表达水平(均P<0.05);基于TCGA‐BLCA队列构建了9个基因(APOBEC3G、CD96、CLEC2D、GNG2、GNLY、IL32、PSMB9、RORA、SKAP1)的膀胱癌DPCs相关基因评分系统。TCGA‐BLCA队列、GSE13507队列和GSE32894队列分析结果显示,高风险评分组膀胱癌患者的总生存期明显比低DPCs评分组短(均P<0.01)。免疫抑制、雌激素等信号通路在高风险评分组中显著富集。结论DPCs与膀胱癌不良预后密切相关,基于DPCs特征基因构建的模型可较准确地预测膀胱癌患者的临床预后。

Objective To investigate the effect of CD45^(+)CD326^(+) double positive cells(DPCs)on the prognosis of bladder cancer(BLCA),to construct a scoring system for bladder cancer DPCs‐related genes,and to explore the characteristics of tumor microenvironment in bladder cancer patients with different DPCs scores.Methods Single‐cell sequencing technology was used to analyze the molecular characteristics of DPCs,and mass cytometry was used to analyze the heterogeneity of the tumor microenvironment in patients with high and low proportions of DPCs.Based on the TCGA‐BLCA cohort,a scoring system was constructed according to the characteristic genes of DPCs and validated in the GSE13507 cohort and the GSE32894 cohort.Results The prognosis of bladder cancer patients in the high DPCs proportion group was worse than that of patients in the low DPCs proportion group,the tumor microenvironment of patients in the high proportion and low proportion group was heterogeneous,and the immune cells and tumor cells of patients in the low DPCs proportion group had higher expression levels of immune checkpoints,co‐inhibitors and coactivators(all P<0.05).A scoring system for bladder cancer with 9 DPCS‐related genes was constructed based on TCGA‐BLCA cohort(APOBEC3G,CD96,CLEC2D,GNG2,GNLY,IL32,PSMB9,RORA,SKAP1).The results of TCGA‐BLCA cohort,GSE13507 cohort and GSE32894 cohort showed that the overall survival of bladder cancer patients in the high DPCs score group was significantly shorter than that of patients in the low DPCs score group(all P<0.01),and the signaling pathways such as immunosuppression and estrogen were significantly enriched in the high‐riskscoregroup.Conclusions DPC sareclosely related to the poorprognosis of bladdercancer,and the model basedon the characteristic gene of DPCs can accurately predict the clinical prognosis of bladder cancer patients.