Zhang Xiaowei, Dai Shuhong, Li Liang, Wang Pengyun, Dong Mingxin
Department of Medicinal Chemistry, School of Pharmacy, Qingdao University, Qingdao, Shandong 266023, P.R. China.
Department of Orthopedics, Zibo Central Hospital, Zibo, Shandong 255036, P.R. China.
Oncol Lett. 2024 Oct 21;29(1):15. doi: 10.3892/ol.2024.14761. eCollection 2025 Jan.
The aim of the present study was to investigate the association between UL16 binding protein 1 (ULBP1) and the prognosis of patients with and immune cell infiltration in breast cancer (BRCA). The mRNA data of BRCA and immune-related genes were extracted from The Cancer Genome Atlas and were analyzed using bioinformatics tools. Subsequently, the results obtained by bioinformatics were validated through the collection of clinical patient data at the Zibo Central hospital (Zibo, China). The difference in the expression of the ULBP1 gene between BRCA tissues and normal precancerous tissues was analyzed, followed by validation using immunohistochemistry. By combining clinical data from patients with BRCA, the prognostic and diagnostic significance of the ULBP1 gene in patients with BRCA was analyzed. Gene enrichment analysis was conducted to gain insight into the molecular mechanisms underlying the regulatory role of ULBP1 in BRCA by analyzing its related functions and signaling pathways. Furthermore, single sample gene set enrichment analysis (ssGSEA) and Spearman's correlation analysis were performed to explore the correlation between ULBP1 as a target gene related with tumor immune cell infiltration. The data revealed that ULBP1 is a target gene associated with immunity and the prognosis of patients with BRCA. Patients with BRCA with a high expression of ULBP1 had a poorer prognosis. ULBP1 expression correlated with progesterone receptor expression, estrogen receptor expression and histological type in patients with BRCA; thus, it may serve as an independent predictor for the overall survival rate of patients. Functional enrichment analysis revealed a significant co-expression between ULBP1 and ULBP2, ULBP3, retinoic acid early transcript 1K, as well as a significant enrichment of pathways associated with carcinogenesis and immune suppression. ssGSEA and Spearman's correlation analysis demonstrated significant correlations between ULBP1 expression and tumor immune cells, as well as immune checkpoints. Overall, the present study demonstrated that ULBP1 was associated with BRCA immunity and might serve as a prognostic and diagnostic biomarker for patients with BRCA. In addition, it might also be a potential target for the immunotherapy of BRCA.
本研究旨在探讨UL16结合蛋白1（ULBP1）与乳腺癌（BRCA）患者预后及免疫细胞浸润之间的关联。从癌症基因组图谱中提取BRCA和免疫相关基因的mRNA数据，并使用生物信息学工具进行分析。随后，通过收集淄博市中心医院（中国淄博）的临床患者数据，对生物信息学所得结果进行验证。分析BRCA组织与癌前正常组织中ULBP1基因表达的差异，随后采用免疫组织化学进行验证。结合BRCA患者的临床数据，分析ULBP1基因在BRCA患者中的预后及诊断意义。通过分析其相关功能和信号通路，进行基因富集分析，以深入了解ULBP1在BRCA中调节作用的分子机制。此外，进行单样本基因集富集分析（ssGSEA）和Spearman相关性分析，以探讨作为与肿瘤免疫细胞浸润相关的靶基因ULBP1之间的相关性。数据显示，ULBP1是与BRCA患者免疫及预后相关的靶基因。ULBP1高表达的BRCA患者预后较差。ULBP1表达与BRCA患者的孕激素受体表达、雌激素受体表达及组织学类型相关；因此，它可能作为患者总生存率的独立预测指标。功能富集分析显示ULBP1与ULBP2、ULBP3、视黄酸早期转录本1K之间存在显著共表达，以及与致癌作用和免疫抑制相关的通路显著富集。ssGSEA和Spearman相关性分析表明ULBP1表达与肿瘤免疫细胞以及免疫检查点之间存在显著相关性。总体而言，本研究表明ULBP1与BRCA免疫相关，可能作为BRCA患者的预后和诊断生物标志物。此外，它也可能是BRCA免疫治疗的潜在靶点。
