Munir Hadia, Rana Ayesha Tassaduque, Faheem Muhammad, Almutairi Saeedah Musaed, Siddique Tehmina, Asghar Samra, Abdel-Maksoud Mostafa A, Mubarak Ayman, Elkhamisy Fatma Alzahraa A, Studenik Christian R, Yaz Hamid
Akhtar Saeed Medical and Dental College Pakistan.
Allama Iqbal Medical College Lahore, Pakistan.
Am J Transl Res. 2022 Jun 15;14(6):3638-3657. eCollection 2022.
Using different online available databases and Bioinformatics tools, we extensively studied the role STAT1 across different cancers.
STAT1 mRNA, protein expression, and promoter methylation were analyzed and validated using UALCAN, GENT2, Human Protein Atlas (HPA), and MEXPRESS. Furthermore, the potential prognostic values were evaluated through KM plotter. Then, cBioPortal was utilized to examine the STAT1-related genetic mutations, while pathway enrichment analysis was performed using DAVID. To identify STAT1 targeted microRNAs (miRNAs) and transcription factors (TFs) we used Enricher. Moreover, a correlational analysis between STAT1 expression tumor purity and CD8+ T immune cells and a gene-drug interaction network analysis was performed using TIMER, CTD, and Cytoscape.
In 23 major human cancers, STAT1 expression was notably up-regulated relative to corresponding controls. As well, the elevated expression of STAT1 was exclusively found to be associated with the reduced overall survival (OS) of Esophageal Carcinoma (ESCA), Kidney Renal Clear Cell Carcinoma (KIRC), and Lung adenocarcinoma (LUAD) patients. This implies that STAT1 plays a significant role in the development and progression of these three cancers. Further pathway analysis indicated that STAT1 enriched genes were involved in six critical pathways, while a few interesting correlations were also documented between STAT1 expression and promoter methylation level, tumor purity, CD8+ T immune cells infiltration, and genetic alteration. In addition, we have also predicted a few miRNAs, TFs, and chemotherapeutic drugs that could regulate the STAT1 expression.
The current study revealed the shared oncogenic, diagnostic, and prognostic role of STAT1 in ESCA, KIRC, and LUAD.
利用不同的在线可用数据库和生物信息学工具，我们广泛研究了信号转导和转录激活因子1（STAT1）在不同癌症中的作用。
使用UALCAN、GENT2、人类蛋白质图谱（HPA）和MEXPRESS分析并验证STAT1信使核糖核酸（mRNA）、蛋白质表达和启动子甲基化。此外，通过KM绘图仪评估潜在的预后价值。然后，利用cBioPortal检查与STAT1相关的基因突变，同时使用DAVID进行通路富集分析。为了识别STAT1靶向的微小核糖核酸（miRNA）和转录因子（TF），我们使用了Enricher。此外，使用TIMER、CTD和Cytoscape进行了STAT1表达、肿瘤纯度与CD8 + T免疫细胞之间的相关性分析以及基因 - 药物相互作用网络分析。
在23种主要人类癌症中，相对于相应对照，STAT1表达显著上调。同样，仅发现STAT1表达升高与食管癌（ESCA）、肾透明细胞癌（KIRC）和肺腺癌（LUAD）患者的总生存期（OS）降低相关。这意味着STAT1在这三种癌症的发生和发展中起重要作用。进一步的通路分析表明，STAT1富集的基因参与了六个关键通路，同时在STAT1表达与启动子甲基化水平、肿瘤纯度、CD8 + T免疫细胞浸润和基因改变之间也记录了一些有趣的相关性。此外，我们还预测了一些可以调节STAT1表达的miRNA、TF和化疗药物。
当前研究揭示了STAT1在ESCA、KIRC和LUAD中的共同致癌、诊断和预后作用。
