目的 探讨自然杀伤细胞2组成员D(NKG2D)的配体UL16结合蛋白(ULBP1)在泛癌中的表达,以及与前列腺癌预后、临床病理、免疫浸润的相关性.方法 本研究通过癌症基因组图谱(TCGA)数据库下载癌症基因组图谱,对不同肿瘤的癌旁及癌配对样本中的ULBP1表达水平进行分析和比较,展示其在33种肿瘤中的变化情况.评估ULBP1在预测泛癌OS、疾病特异性生存期(DSS)和无进展生存期(PFS)中的意义.借助TIMER2数据库,进行免疫细胞浸润相关性分析.通过绘制受试者操作特征曲线(ROC曲线),评估ULBP1表达在前列腺癌中的诊断价值.应用"Wilcoxon signed rank test"、Spearman 相关性分析,Mann-Whitney U 检验及 Cox 回归进行数据分析.结果 ULBP1在肾上腺皮质癌、多形性胶质母细胞瘤、膀胱尿路上皮癌、乳腺浸润性癌、前列腺腺癌等33种癌症类型中呈现出显著的差异性表达态势,膀胱尿路上皮癌癌组高于癌旁组(0.91比0.13,t=0.87,P＜0.01);乳腺浸润性癌癌组高于癌旁组(0.97比0.25,t=0.91,P＜0.01);胆管癌(CHOL)癌组高于癌旁组(1.80比0.06,t=0.90,P＜0.01);结肠腺癌(COAD)癌组高于癌旁组(0.63 比 0.07,t=0.91,P＜0.01);前列腺腺癌癌组高于癌旁组(0.36 比 0.12,t=0.93,P＜0.01)等15种肿瘤,ULBP1的表达水平癌组织中高于正常组织中;无进展生存期(PFS)分析显示ULBP1是PRAD(风险比(HR)=1.66,95％可信区间(CI):1.09～2.52,P＜0.05)的危险因子.免疫分析表明,ULBP1与PRAD的CD8+T细胞、巨噬细胞、辅助性T细胞、中央记忆型T细胞、Th2细胞(r=0.10、0.22、0.30、0.12、0.28,P＜0.01)呈正相关.与 NK 细胞、肥大细胞、Th1 细胞(r=-0.30、-0.24、-0.12,P＜0.01)呈负相关.结论 ULBP1在前列腺癌中与预后、免疫浸润及TP53突变密切相关.
The pan-cancer analysis of natural killer group 2 member D ligand UL16 binding protein 1 and its correlation with prognosis and immune infiltration in prostate cancer
Objective To investigate the expression of the natural killer group 2 member D(NKG2D)ligand UL16 binding protein 1(ULBP1)in pan-cancer and its correlation with prognosis,clini-copathological features,and immune infiltration in prostate cancer.Methods This study utilized cancer gene expression profiles obtained from the the cancer genome atlas(TCGA)database and analyzed and compared the expression levels of ULBP1 in adjacent and paired tumor samples from different tumors,showing its changes in 33 types of tumors.The study evaluated the significance of ULBP1 in predicting o-verall survival(OS),disease-specific survival(DSS),and progression-free survival(PFS)in cancer.It also conducted an immune cell infiltration-related analysis using the TIMER2 database.The study assessed the diagnostic value of ULBP1 expression in prostate cancer by drawing receiver operating characteristic(ROC)curves.Data analysis was conducted using the"Wilcoxon signed rank test",Spearman correlation analysis,Mann-Whitney U test,and Cox regression.Results The expression of ULBP1 in 33 cancer types,such as adrenocortical carcinoma,glioblastoma multiforme,bladder urothelial carcinoma,breast in-vasive carcinoma and prostate adenocarcinoma,showed a significant difference.The cancer group of blad-der urothelial carcinoma was higher than the adjacent group(0.91 vs.0.13,t=0.87,P＜0.01).The in-vasive breast cancer group was higher than the adjacent group(0.97 vs.0.25,t=0.91,P＜0.01).Cholangiocarcinoma(CHOL)was higher in cancer group than in adjacent cancer group(1.80 vs.0.06,t=0.90,P＜0.01).Colon adenocarcinoma(COAD)in cancer group was higher than that in adjacent cancer group(0.63 vs.0.07,t=0.91,P＜0.01).The expression level of ULBP1 in prostate adenocarci-noma group was higher than that in the adjacent group(0.36 vs.0.12,t=0.93,P＜0.01).Among 15 kinds of tumors,the expression level of ulbp1 in cancer tissue group was higher than that in normal tissue group.Progression-free survival(PFS)analysis indicates that ULBP1 serves as a risk factor for PRAD[hazard ratio(HR)=1.66,95％CI:1.09-2.52,P＜0.05].Furthermore,immunological analyses reveal a positive correlation between ULBP1 and CD8+T cells,macrophages,helper T cells,central memory T cells,and Th2 cells specific to PRAD(r=0.10,0.22,0.30,0.12,0.28,P＜0.01),while exhibiting negative correlations with NK cells,mast cells,and Th1 cells(r=-0.30,-0.24,-0.12,P＜0.01).High ULBP1 expression in prostate cancer demonstrated good diagnostic value and was closely associated with TP53 mutation status.Conclusion ULBP1 is closely related to prognosis,immune infiltration,and TP53 mutation in prostate cancer,suggesting that ULBP1 could serve as a potential diagnostic and prognos-tic biomarker.
UL16 binding protein 1Natural killer group 2 member DProstate cancerThe pan-cancer analysis
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