Decoding signal transducer and activator of transcription 1 across various cancers through data mining and integrative analysis

Hadia Munir; Ayesha Tassaduque Rana; Muhammad Faheem; Saeedah Musaed Almutairi; Tehmina Siddique; Samra Asghar; Mostafa A Abdel-Maksoud; Ayman Mubarak; Fatma Alzahraa A Elkhamisy; Christian R Studenik; Hamid Yaz

Decoding signal transducer and activator of transcription 1 across various cancers through data mining and integrative analysis

Am J Transl Res. 2022 Jun 15;14(6):3638-3657. eCollection 2022.

Authors

Affiliations

¹ Akhtar Saeed Medical and Dental College Pakistan.
² Allama Iqbal Medical College Lahore, Pakistan.
³ District Head Quarter Hospital Faisalabad Faisalabad, Pakistan.
⁴ Department of Botany and Microbiology, College of Science, King Saud University Riyadh, P.O. 2455, Riyadh 11451, Saudi Arabia.
⁵ Department of Biotechnology, Faculty of Life Sciences, University of Okara Okara, Pakistan.
⁶ Department of Medical Laboratory Technology, Faculty of Rehablitation and Allied Health Sciences, Riphah International University Faisalabad, Pakistan.
⁷ Pathology Department, Faculty of Medicine, Helwan University Cairo, Egypt.
⁸ Basic Medical Sciences Department, Faculty of Medicine, King Salman International University South Sinai, Egypt.
⁹ Department of Pharmaceutical Sciences, Division of Pharmacology and Toxicology, University of Vienna Vienna, Austria.

PMID: 35836889
PMCID: PMC9274611

Abstract

Objectives: Using different online available databases and Bioinformatics tools, we extensively studied the role STAT1 across different cancers.

Methods: 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.

Results: 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.

Conclusion: The current study revealed the shared oncogenic, diagnostic, and prognostic role of STAT1 in ESCA, KIRC, and LUAD.

Keywords: CD8+ T immune cells; Cancer; OS analysis; STAT1; diagnostic; prognostic.