Ali Liaqat, Raza Abbas Ali, Zaheer Ahmad Bin, Alhomrani Majid, Alamri Abdulhakeem S, Alghamdi Saleh A, Almalki Abdulraheem Ali, Alghamdi Ahmad A, Khawaja Imran, Alhadrami Mai, Ramzan Faiqah, Jamil Muhammad, Ali Mubarik, Jabeen Norina
Department of Urology, Institute of Kidney Diseases, Hayatabad Medical Complex Peshawar 25000, Pakistan.
Surgery Department, Bacha Khan Medical College, MTI Mardan Medical Complex Mardan 23200, Pakistan.
Am J Transl Res. 2023 Jul 15;15(7):4851-4872. eCollection 2023.
The regulation of various cellular functions such as growth, proliferation, metabolism, and angiogenesis, is dependent on the PI3K pathway. Recent evidence has indicated that kidney renal clear cell carcinoma (KIRC) can be triggered by the deregulation of this pathway. The objective of this research was to investigate 25 genes associated with activation of the PI3K pathway in KIRC and control samples to identify four hub genes that might serve as novel molecular biomarkers and therapeutic targets for treating KIRC.
Multi-omics in silico and in vitro analysis was employed to find hub genes related to the PI3K pathway that may be biomarkers and therapeutic targets for KIRC.
Using STRING software, a protein-protein interaction (PPI) network of 25 PI3K pathway-related genes was developed. Based on the degree scoring method, the top four hub genes were identified using Cytoscape's Cytohubba plug-in. TCGA datasets, KIRC (786-O and A-498), and normal (HK2) cells were used to validate the expression of hub genes. Additionally, further bioinformatic analyses were performed to investigate the mechanisms by which hub genes are involved in the development of KIRC. Out of a total of 25 PI3K pathway-related genes, we developed and validated a diagnostic and prognostic model based on the up-regulation of TP53 (tumor protein 53) and CCND1 (Cyclin D1) and the down-regulation of PTEN (Phosphatase and TENsin homolog deleted on chromosome 10), and GSK3B (Glycogen synthase kinase-3 beta) hub genes. The hub genes included in our model may be a novel therapeutic target for KIRC treatment. Additionally, associations between hub genes and infiltration of immune cells can enhance comprehension of immunotherapy for KIRC.
We have created a new diagnostic and prognostic model for KIRC patients that uses PI3K pathway-related hub genes (TP53, PTEN, CCND1, and GSK3B). Nevertheless, further experimental studies are required to ascertain the efficacy of our model.
各种细胞功能（如生长、增殖、代谢和血管生成）的调节依赖于PI3K通路。最近的证据表明，该通路的失调可引发肾透明细胞癌（KIRC）。本研究的目的是调查KIRC和对照样本中与PI3K通路激活相关的25个基因，以鉴定四个可能作为KIRC新型分子生物标志物和治疗靶点的核心基因。
采用多组学的计算机模拟和体外分析方法，寻找与PI3K通路相关的核心基因，这些基因可能是KIRC的生物标志物和治疗靶点。
使用STRING软件构建了25个PI3K通路相关基因的蛋白质-蛋白质相互作用（PPI）网络。基于度评分法，使用Cytoscape的Cytohubba插件鉴定出前四个核心基因。利用TCGA数据集、KIRC（786-O和A-498）细胞以及正常（HK2）细胞来验证核心基因的表达。此外，进行了进一步的生物信息学分析，以研究核心基因参与KIRC发生发展的机制。在总共25个PI3K通路相关基因中，我们基于肿瘤蛋白53（TP53）和细胞周期蛋白D1（CCND1）的上调以及第10号染色体缺失的磷酸酶及张力蛋白同源物（PTEN）和糖原合酶激酶-3β（GSK3B）核心基因的下调，开发并验证了一个诊断和预后模型。我们模型中包含的核心基因可能是KIRC治疗的新型治疗靶点。此外，核心基因与免疫细胞浸润之间的关联可以增强对KIRC免疫治疗的理解。
我们为KIRC患者创建了一个新的诊断和预后模型，该模型使用PI3K通路相关的核心基因（TP53、PTEN、CCND1和GSK3B）。然而，需要进一步的实验研究来确定我们模型的有效性。
