Extramammary Paget’s disease (EMPD) is an intra-epidermal adenocarcinoma. Till now, the mechanisms underlying the pathogenesis of scrotal EMPD is poorly known. This present study aims to explore the knowledge of molecular mechanism of scrotal EMPD by identifying the hub genes and candidate drugs using integrated bioinformatics approaches. Firstly, the microarray datasets (GSE117285) were downloaded from the GEO database and then analyzed using GEO2R in order to obtain differentially expressed genes (DEGs). Moreover, hub genes were identified on the basis of their degree of connectivity using Cytohubba plugin of cytoscape tool. Finally, GEPIA and DGIdb were used for the survival analysis and selection of therapeutic candidates, respectively. A total of 786 DEGs were identified, of which 10 genes were considered as hub genes on the basis of the highest degree of connectivity. After the survival analysis of ten hub genes, a total of 5 genes were found to be altered in EMPD patients. Furthermore, 14 drugs of CHEK1, CCNA2, and CDK1 were found to have therapeutic potential against EMPD. This study updates the information and yields a new perspective in the context of understanding the pathogenesis of EMPD. In future, hub genes and candidate drugs might be capable of improving the personalized detection and therapies for EMPD.
In the present work, a mechanism was proposed to explain the progression in the pathogenesis of EMPD. It might due to the genes that disturb the cellular pathways which ultimately leads to the disease condition. This research discerned hub genes as key biological markers and their associated pathways involved in the development of EMPD. Based on our knowledge, CHEK1, CCNA2, and CDK1 have not been previously reported to be related to EMPD. It was found that these genes might act as potential biomarkers for the diagnosis of EMPD at an early stage. Our findings reveal that EMPD causes disruption in cellular pathways which unfortunately makes the disease condition much worse. In the near future, further study and clinical trials are required for the identification of genes and small drug-like molecules having effective diagnostic and prognostic value, respectively. Our research will serve as a significant pioneer for the researchers who want to identify the associated pathways involved in the pathogenesis of EMPD. This research relies on various freely available databases to shed light on EMPD pathogenesis and treatment. In vivo and in vitro investigations of genes and pathways interaction are essential to delineate the specific roles of the identified genes, which could confirm gene functions and reveal the mechanisms underlying EMPD. In the future, additional experimental research on these hub genes could lead to an increase in our knowledge to fight against EMPD by means of novel therapeutic approaches. Based on the hub genes, experimental models may be designed in terms of the detection of pathogenesis, evaluation of risk, and determining the targeted therapies of EMPD.
Authors: Fatima Noor, Muhammad Hamzah Saleem, Jen-Tsung Chen, Muhammad Rizwan Javed, Wafa Abdullah Al-Megrin, Sidra Aslam