In Silico Analysis of Prostate Cancer

Despite its high incidence, prostate cancer is still not clearly understood. Early detection of the disease increases its treatability, however the current detection methods employed are unspecific and unreliable. As it progresses, it builds resistance to anti-cancer medicines, hence the interest in exploring alternative compounds to hinder further advancement. To address these, this study aims to establish genetic markers that help elucidate molecular mechanisms involved in prostate cancer advancement and identify natural compounds and repurposed drugs that may potentially inhibit P300, a pro-oncogenic protein. Meta-analysis was performed on GSE17951, GSE46602, and GSE69223 using metaMA and RankProd. Common differentially expressed genes (DEGs) found in both results are considered the paper's DEGs. Hub gene identification was done through Cytoscape plug-ins. With an FDR cut-off of 0.01 for metaMA and 0.01 percentage of false positive and logFC |0.5| for RankProd, a total of 935 genes were common between them - 386 of which are overexpressed. The hub genes are BIRC5, BUB1B, CCNB1, CCNB2, CDK1, HMMR, MAD2L1, NUSAP1, PBK, RRM2, TTK, and ZWINT, which are significantly associated with the cell cycle. BUB1B may be a driving force in disease advancement considering its role in regulation of mitotic spindle and the PLK1 pathway. In analyzing the cell cycle pathway, P300 is revealed to be a promising therapeutic target given its contribution to cancer advancement by regulating p53 and AR signaling. Literature search yielded ten natural compounds, while ten compounds each of prostate cancer-specific and repurposed drugs were also docked to the protein. Docking was conducted on AutoDock, employing its Lamarckian Genetic Algorithm. Among the natural compounds, Fisetin had the highest affinity at -9.18 kcal/mol. Abiraterone acetate, a prostate cancer-specific drug, scored the highest in its group with an affinity of -10.68 kcal/mol; lastly, Nelfinavir had the best affinity among all compounds docked to the protein with an affinity of -11.93 kcal/mol. Additionally, Nelfinavir mirrored four of the five key binds that the control ligand has with the protein, further showing its high compatibility with the receptor and its potential in inhibiting the protein in in vitro experiments.