Department of Urology, the Second Affiliated Hospital of Soochow University, Suzhou, China.
Department of Pathology, Children's Hospital of Soochow University, Suzhou, China.
Front Immunol. 2024 Jul 30;15:1442555. doi: 10.3389/fimmu.2024.1442555. eCollection 2024.
cGMP-dependent protein kinase 1 (PRKG1) has shown to be associated with some tumorigenesis, while the role of PRKG1 in bladder cancer is unclear.
To investigate the biological and clinical significance of PRKG1 in bladder cancer, we detected the expression of PRKG1 and explored the function of PRKG1 in bladder cancer cells. The PRKG1 transcripts data was downloaded from The Cancer Genome Atlas (TCGA) database, and immunohistochemistry staining was conducted on formalin-fixed paraffin-embedded (FFPE) sample tissues. Relationship between clinical characteristics of patients and expression of PRKG1 was analyzed in FFPE samples, TCGA database, and GSE19423 dataset. PRKG1 was over-expressed, and cell proliferation, migration, invasion, apoptosis, and spheroidizing ability were then detected. Chemosensitivity to cisplatin was detected with cell viability, and half-maximal drug inhibitory concentration (IC50) was calculated. In addition, the relation between PRKG1 expression and the infiltration level of tumor immune cells in tumor microenvironment were analyzed.
The results showed expression of PRKG1 was lower in bladder cancer, compared with normal tissues both at protein and transcript levels. Lower PRKG1 expression was related to higher tumor grade, T stage, and muscle invasion, also predicted worse overall survival and recurrence free survival in patients treated with Bacillus Calmette-Guerin (BCG) intravesical immunotherapy. Analysis of tumor immune cells infiltration showed lower PRKG1 was associated with non-inflamed tumor microenvironment.
The present study firstly identified the anti-tumor role and tumor immune regulatory role of PRKG1, also found loss of PRKG1 could be used as a prognosis factor. The present study provided a potential biomarker and therapy target to bladder cancer.
环鸟苷酸依赖的蛋白激酶 1(PRKG1)已被证明与一些肿瘤发生有关,而 PRKG1 在膀胱癌中的作用尚不清楚。
为了研究 PRKG1 在膀胱癌中的生物学和临床意义,我们检测了 PRKG1 的表达,并探索了 PRKG1 在膀胱癌细胞中的功能。从癌症基因组图谱(TCGA)数据库中下载 PRKG1 转录本数据,并对福尔马林固定石蜡包埋(FFPE)样本组织进行免疫组织化学染色。在 FFPE 样本、TCGA 数据库和 GSE19423 数据集分析了患者的临床特征与 PRKG1 表达之间的关系。过表达 PRKG1 后,检测细胞增殖、迁移、侵袭、凋亡和球体形成能力。用细胞活力检测顺铂的化疗敏感性,并计算半最大药物抑制浓度(IC50)。此外,还分析了 PRKG1 表达与肿瘤微环境中肿瘤免疫细胞浸润水平之间的关系。
结果显示,PRKG1 在膀胱癌中的表达低于正常组织,无论是在蛋白水平还是转录水平。较低的 PRKG1 表达与较高的肿瘤分级、T 分期和肌肉浸润有关,也预示着接受卡介苗膀胱内免疫治疗的患者总体生存率和无复发生存率较差。肿瘤免疫细胞浸润分析表明,较低的 PRKG1 与非炎症性肿瘤微环境有关。
本研究首次确定了 PRKG1 的抗肿瘤作用和肿瘤免疫调节作用,还发现 PRKG1 的缺失可作为预后因素。本研究为膀胱癌提供了一个潜在的生物标志物和治疗靶点。