■cGMP依赖性蛋白激酶1(PRKG1)已显示与一些肿瘤发生有关,而PRKG1在膀胱癌中的作用尚不清楚。
■探讨PRKG1在膀胱癌中的生物学和临床意义,我们检测了PRKG1的表达,并探讨了PRKG1在膀胱癌细胞中的功能。PRKG1转录本数据从癌症基因组图谱(TCGA)数据库下载,对福尔马林固定的石蜡包埋(FFPE)样品组织进行免疫组织化学染色。分析患者临床特征与FFPE标本中PRKG1表达的关系,TCGA数据库,和GSE19423数据集。PRKG1过表达,和细胞增殖,迁移,入侵,凋亡,然后检测球化能力。细胞活力检测到对顺铂的化学敏感性,并计算半数最大药物抑制浓度(IC50)。此外,分析PRKG1表达与肿瘤微环境中肿瘤免疫细胞浸润水平的关系。
■结果显示PRKG1在膀胱癌中表达较低,在蛋白质和转录水平上与正常组织相比。较低的PRKG1表达与较高的肿瘤分级有关,T级,和肌肉入侵,在接受卡介苗(BCG)膀胱内免疫治疗治疗的患者中,还预测总体生存率和无复发生存率会降低.对肿瘤免疫细胞浸润的分析显示,较低的PRKG1与非发炎的肿瘤微环境有关。
■本研究首次确定了PRKG1的抗肿瘤作用和肿瘤免疫调节作用,也发现PRKG1的缺失可以作为预后因素。本研究为膀胱癌提供了潜在的生物标志物和治疗靶点。
UNASSIGNED: cGMP-dependent protein kinase 1 (PRKG1) has shown to be associated with some tumorigenesis, while the role of PRKG1 in bladder cancer is unclear.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.