Identification of Potential Key Genes in Prostate Cancer with Gene Expression, Pivotal Pathways and Regulatory Networks Analysis Using Integrated Bioinformatics Methods

Prostate cancer (PCa) is the most prevalent cancer (20%) in males and is accountable for a fifth (6.8%) cancer-related deaths in males globally. Smoking, obesity, race/ethnicity, diet, age, chemicals and radiation exposure, sexually transmitted diseases, etc. are among the most common risk factors f...

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Main Authors: Mohd Mabood Khan, Mohammad Taleb Mohsen, Md. Zubbair Malik, Sali Abubaker Bagabir, Mustfa F. Alkhanani, Shafiul Haque, Mohammad Serajuddin, Mausumi Bharadwaj
Format: Article
Language:English
Published: MDPI AG 2022-04-01
Series:Genes
Subjects:
Online Access:https://www.mdpi.com/2073-4425/13/4/655
Description
Summary:Prostate cancer (PCa) is the most prevalent cancer (20%) in males and is accountable for a fifth (6.8%) cancer-related deaths in males globally. Smoking, obesity, race/ethnicity, diet, age, chemicals and radiation exposure, sexually transmitted diseases, etc. are among the most common risk factors for PCa. However, the basic change at the molecular level is the manifested confirmation of PCa. Thus, this study aims to evaluate the molecular signature for PCa in comparison to benign prostatic hyperplasia (BPH). Additionally, representation of differentially expressed genes (DEGs) are conducted with the help of some bioinformatics tools like DAVID, STRING, GEPIA, Cytoscape. The gene expression profile for the four data sets GSE55945, GSE104749, GSE46602, and GSE32571 was downloaded from NCBI, Gene Expression Omnibus (GEO). For the extracted DEGs, different types of analysis including functional and pathway enrichment analysis, protein–protein interaction (PPI) network construction, survival analysis and transcription factor (TF) prediction were conducted. We obtained 633 most significant upregulated genes and 1219 downregulated genes, and a sum total of 1852 DEGs were found from all four datasets after assessment. The key genes, including <i>EGFR</i>, <i>MYC</i>, <i>VEGFA</i>, and <i>PTEN</i>, are targeted by TF such as AR, Sp1, TP53, NF-KB1, STAT3, RELA. Moreover, miR-21-5p also found significantly associated with all the four key genes. Further, The Cancer Genome Atlas data (TCGA) independent database was used for validation of key genes <i>EGFR</i>, <i>MYC</i>, <i>VEGFA</i>, PTEN expression in prostate adenocarcinoma. All four key genes were found to be significantly correlated with overall survival in PCa. Therefore, the therapeutic target may be determined by the information of these key gene’s findings for the diagnosis, prognosis and treatment of PCa.
ISSN:2073-4425