北京大学学报(医学版) ›› 2023, Vol. 55 ›› Issue (5): 793-801. doi: 10.19723/j.issn.1671-167X.2023.05.004
Huan-rui LIU1,Xiang PENG1,2,Sen-lin LI1,Xin GOU1,*()
摘要:
目的: 探讨HER-2相关基因(the human epidermal growth factor receptor-2-related genes, HRGs)与膀胱癌生存预后的相关性,并基于HRGs构建一种膀胱癌患者生存预后的预测模型。方法: 从癌症基因组图谱(the cancer genome atlas, TCGA)中下载膀胱肿瘤组织mRNA测序数据和临床数据,通过与分子签名数据库(the molecular signatures database, MSigDB)中HER-2相关的基因联合分析鉴定膀胱癌中的HRGs。利用单因素和多因素Cox回归分析进一步明确与膀胱癌生存相关的HRGs(P < 0.05),并构建HRGs风险模型(HRGs risk score model, HRSM),根据风险评分取中位数将膀胱癌患者分成高风险组和低风险组。利用R语言对高风险和低风险组的患者进行生存分析,并对HRGs与临床特征的相关性进行分析。利用多因素Cox回归分析,验证影响膀胱癌患者预后的独立因素。计算HRSM的受试者工作特征曲线(receiver operating characteristic curve, ROC)下的面积(area under the curve, AUC),并构建诺模图(nomogram)对膀胱癌患者进行生存预测。利用TIMER数据库对HRSM和患者免疫细胞浸润相关性进行分析。结果: 共鉴定到13个与患者生存相关的HRGs。通过多因素Cox回归分析,筛选出5个基因(BTC、CDC37、EGF、PTPRR和EREG)构建HRSM,高风险组的膀胱癌患者5年生存率明显低于低风险组患者。通过临床相关性分析发现,PTPRR的高表达与肿瘤分级、分期呈显著负相关,而EREG的高表达与肿瘤分级、分期呈正相关;EGF表达量的增加和患者的高级别有相关性,而CDC37的高表达却呈现出了相反的结果;BTC的表达与临床特征无显著相关性。通过对HRSM与免疫细胞的相关性分析发现,风险评分与树突状细胞、CD8+T细胞、CD4+T细胞、中性粒细胞和巨噬细胞的浸润呈正相关。结论: HRGs对膀胱癌患者的预后有重要作用,可能作为新的预测性生物标志物和治疗的潜在靶点。
中图分类号:
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