Identification of differentially expressed genes and drug targets in prostate cancer using next-generation sequencing analysis and docking
摘要
Prostate cancer, a leading malignancy with significant impact on men’s health, was the focus of this study, which aimed to identify candidate genes through differential gene expression analysis using Galaxy, an open-source platform for analyzing next-generation sequencing (NGS) data. RNA sequencing (RNA-Seq) analysis was performed on several datasets from the GEO database we conducted to understand the underlying mechanisms involving 15 patients, including 7 tumor conditions and 8 control. A total of 505 significantly upregulated differentially expressed genes (DEGs) were identified based on the threshold criteria of log fold change (LogFC) ≥ 1.5 and a p-value < 0.05. Pathway analysis revealed the involvement of key genes involved in the pathways. These pathways are crucial for cancer progression and metastasis. The protein–protein interactions (PPI) network analysis identified significant key hub genes including PLA2G2F, PLA2G2D, PLA2G1B, PLA2G10, PLA2G5, PLA2G3, LPCAT4, PLB1, PLA2G12A, and PLA2G2E using the STRING database, visualized through Cytoscape. The network analysis highlighted key hub genes involved in critical pathways, with clustering coefficients indicating the reliability of interactions. PCa-phytochemical complex docking analysis using PyRx software demonstrated significant binding affinities of phytochemicals. Notably, the phytochemical epigallocatechin gallate shows binding affinity with more than one PCa proteins: 1KQU, 1TRN, 3U8H, 5WZM, 5WZO, and 5WZT with docking score of −8.7, −7.7, −8.8, −9, −8.6, and −8.1, respectively. The lycopene shows binding free energy of −7.1 kcal/mol with 3U8H. Phytochemical toxicity analysis using ProTox-II predicted toxicity levels, indicating lycopene as a lead compound with low toxicity and inactive organ-specific toxicity, suggesting it could be a promising drug candidate for PCa treatment.