DPH2在前列腺癌中的免疫浸润及预后预测的研究

A Study of DPH2 as a Prognosis Prediction and Its Correlationwith Immune Infiltrates in Prostate Cancer

目的 白磺酰胺生物合成蛋白2(DPH2)基因是白喉毒素靶标白硫胺生物合成的关键酶,它对前列腺癌患者的预后和免疫浸润的影响尚不清楚,探讨其在前列腺癌中的免疫浸润及预后预测中作用。方法 从癌症基因组图谱(TCGA)数据库中获得的前列腺癌患者的表达谱和临床信息。使用Wilcoxon秩和检验,比较前列腺癌和正常前列腺组织之间的DPH2表达水平。进行功能富集分析以探索所涉及的潜在信号通路和生物学功能。使用单样本基因集富集分析评估免疫细胞浸润。UALCAN数据库用于分析DPH2的甲基化状态。采用Kaplan-Meier方法和Cox回归分析确定DPH2的预后价值。构建列线图以预测癌症诊断后1年、3年和5年的复发转移率。结果 DPH2在前列腺癌中过表达,与T分期(P=0.013)、N分期(P=0.025)、PFI事件(P=0.023)和OS(P<0.001)显著相关。DPH2过表达导致OS和疾病特异性生存率显著下降。多变量Cox分析将DPH2确定为OS的独立预后标志物。同样,DPH2的低甲基化状态也与预后不良有关。功能富集分析表明,富集途径包括葡萄糖醛酸盐代谢过程、脱氧核糖核酸-结合转录激活物RNA活性、特异的聚合酶Ⅱ、细胞周期、细胞衰老和卵母细胞减数分裂。此外,DPH2的过表达与自然杀伤细胞、Mast细胞、Th1细胞和浆细胞样树突状细胞的免疫细胞浸润水平呈负相关。结论 DPH2可能是一种新型的预后生物标志物,在前列腺癌的免疫浸润中起重要作用。

Objective White sulfonamide biosynthetic protein 2(DPH2)gene is the key enzyme of diphtheria toxin target leukothiamine biosynthesis,but its effects on the prognosis and immune infiltration of patients with prostate cancer remains unclear.Methods In this study,the expression profiles and clinical information of prostate cancer patients were obtained from the Cancer Genome Map(TCGA)database.Wilcoxon rank sum test was used to compare the expression of DPH2 between prostate cancer and normal prostate tissue.Functional enrichment analysis was conducted to explore the potential regulatory signal pathways and related biological functions involved.Single sample gene cluster enrichment analysis was applied to evaluate immune cell infiltration.UALCAN database was utilized to analyze the methylation status of DPH2.The prognostic value of DPH2 was determined by Kaplan Meier method and Cox regression analysis.A line chart was constructed to predict recurrence and metastasis rates at one,three,or five years after cancer diagnosis.Results The overexpression of DPH2 in prostate cancer was significantly correlated with T stage(P<0.013),N stage(P<0.025),PFI event(P<0.023)and OS(P<0.001).Overexpression of DPH2 resulted in a significant decrease in OS and disease-specific survival rates.Multivariate Cox analysis identified DPH2 as an independent prognostic marker for OS.Similarly,the hypomethylation status of DPH2 was also associated with the poor prognosis.Functional enrichment analysis showed that the enrichment pathways included glucuronide metabolism,deoxyribonucleic acid binding transcriptional activator RNA activity,specific polymerase Ⅱ,cell cycle,cell senescence and oocyte meiosis.In addition,the overexpression of DPH2 was negatively correlated with the level of immune cell infiltration of natural killer cells,Mast cells,Th1 cells and plasma cell-like dendritic cells.Conclusion Our study suggests that DPH2 could serve as a novel prognostic biomarker and play an important role in immune infiltration of prostate cancer.