Feng Dechao, Zhu Weizhen, Shi Xu, Wei Wuran, Han Ping, Wei Qiang, Yang Lu
Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu 610041, China.
Heliyon. 2022 Sep 29;8(10):e10750. doi: 10.1016/j.heliyon.2022.e10750. eCollection 2022 Oct.
We sought to determine whether leucine zipper protein 2 (LUZP2) could benefit men with prostate cancer (PCa) undergoing radical radiotherapy (RT) or prostatectomy (RP).
Analysis was done on differentiating expression, clinical prognosis, co-expressed genes, immune infiltration, and epigenetic changes. All of our analyses were done using the R software (version 3.6.3) and the appropriate packages.
In terms of PCa, tumor samples expressed LUZP2 more than normal samples did. In the TCGA database and GSE116918, we found that LUZP2 was the only independent risk factor for PCa. The shared enriched pathways for patients undergoing RP or RT were cell-cell adhesion, regulation of filopodium assembly, and extracellular matrix containing collagen. With the exception of TNFRSF14, we discovered that LUZP2 was negatively correlated with 21 immune checkpoints in PCa patients receiving RT. We found a significant inverse relationship between LUZP2 expression and the tumor immune environment, which included B cells, CD4+ T cells, neutrophils, macrophages, dendritic cells, stromal score, immune score, and estimate score, in patients receiving RP or RT. Additionally, tumor purity was positively correlated with LUZP2. We found that the drug bortezomib may be susceptible to the LUZP2. DNA methylation was significantly associated with the mRNA expression of LUZP2 in PCa patients from the TCGA database, and LUZP2 methylation was positively correlated with immune cells. The proliferative activity of various PCa cells, which correlated to different stages of this disease, was also found to be significantly reduced by LUZP2 reduction, according to the results of our experimental work.
We proposed a relatively comprehensive understanding of the roles of LUZP2 on PCa from the fresh perspective of senescence.
我们试图确定亮氨酸拉链蛋白2（LUZP2）是否能使接受根治性放疗（RT）或前列腺切除术（RP）的前列腺癌（PCa）男性患者获益。
对差异表达、临床预后、共表达基因、免疫浸润和表观遗传学变化进行分析。我们所有的分析均使用R软件（版本3.6.3）及相应的软件包完成。
在PCa方面，肿瘤样本中LUZP2的表达高于正常样本。在TCGA数据库和GSE116918中，我们发现LUZP2是PCa的唯一独立危险因素。接受RP或RT的患者共有的富集通路是细胞-细胞黏附、丝状伪足组装的调节以及含胶原蛋白的细胞外基质。除肿瘤坏死因子受体超家族成员14（TNFRSF14）外，我们发现LUZP2与接受RT的PCa患者中的21种免疫检查点呈负相关。我们发现LUZP2表达与接受RP或RT的患者的肿瘤免疫环境之间存在显著的负相关，肿瘤免疫环境包括B细胞、CD4 + T细胞、中性粒细胞、巨噬细胞、树突状细胞、基质评分、免疫评分和估计评分。此外，肿瘤纯度与LUZP2呈正相关。我们发现药物硼替佐米可能对LUZP2敏感。来自TCGA数据库的PCa患者中，DNA甲基化与LUZP2的mRNA表达显著相关，且LUZP2甲基化与免疫细胞呈正相关。根据我们的实验工作结果，LUZP2表达降低也显著降低了与该疾病不同阶段相关的各种PCa细胞的增殖活性。
我们从衰老这一新视角对LUZP2在PCa中的作用提出了相对全面的认识。
