研究动态
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PRKG1在膀胱癌中的临床意义及抗肿瘤作用。

The clinical significance and anti-tumor role of PRKG1 in bladder cancer.

发表日期:2024
作者: Lu Jin, Ting Chen, Huan Sun, Guangcheng Dai, Qiu Yao, Feng Yuan, Xiaolong Liu, Boxin Xue
来源: Frontiers in Immunology

摘要:

cGMP依赖性蛋白激酶1(PRKG1)已被证明与某些肿瘤发生有关,但PRKG1在膀胱癌中的作用尚不清楚。为了探讨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在膀胱癌中的作用。 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,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数据集中分析患者临床特征与PRKG1表达之间的关系。 PRKG1过表达,然后检测细胞增殖、迁移、侵袭、凋亡和球化能力。通过细胞活力检测对顺铂的化疗敏感性,并计算半数最大药物抑制浓度(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的关系。结果显示,与正常组织相比,PRKG1在膀胱癌中的蛋白表达和转录水平表达均较低。较低的 PRKG1 表达与较高的肿瘤分级、T 分期和肌肉侵袭相关,也预示着接受卡介苗 (BCG) 膀胱内免疫治疗的患者总生存期和无复发生存期较差。肿瘤免疫细胞浸润分析显示PRKG1的降低与非炎症的肿瘤微环境相关。本研究首先鉴定了PRKG1的抗肿瘤作用和肿瘤免疫调节作用,同时发现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。版权所有 © 2024 Jin、Chen、Sun、Dai、Yao、Yuan、Liu 和 Xu。
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.Copyright © 2024 Jin, Chen, Sun, Dai, Yao, Yuan, Liu and Xue.