AURKA as a druggable hub gene for treating Vulvovaginal melanomas: in silico study

Melanoma is a highly aggressive neoplasm originating from melanocytes in various anatomical sites within the human body. Vulvar and vaginal melanoma represent subtypes of melanoma primarily impacting the melanocytes in the genital region of women. Despite the low prevalence (۱%), they showed a poor prognosis, exhibiting a specific ۵-year survival rate of ۱۱.۴% among all types of melanomas . Hence, there is a critical need to explore the molecular mechanisms of these two types of melanomas to unveil novel therapeutic strategies that could enhance the survival outcomes associated with these malignancies. Method: In this investigation to identify critical genes in Vulvovaginal melanoma, gene expression profiles of vulvar melanoma and primary cutaneous melanoma tissues (GSE۲۰۸۱۷۲), as well as vaginal melanoma tissues, and adjacent healthy vaginal mucosa (GSE۲۰۸۱۷۳) that were uploaded to NCBI's GEO database were utilized. Then the online GEO۲R tool was applied to identify differentially expressed genes (DEGs) in these microarray datasets. Specifically, genes exhibiting LogFC>۱ and a p-adjusted value of <۰.۰۵ were singled out for further analysis. Furthermore, the biological pathways governed by the upregulated genes were determined through the EnrichR database. Identifying potentially druggable hub genes was accomplished by using resources such as STRING, the Drug Gene Interaction Database (DGIdb), and the Cytoscape software. Results and: Significantly, a total of ۵۴ and ۶۱۱ genes leveled up in vulvar and vaginal melanoma, respectively. Particularly, ۵۲ genes were found to be commonly upregulated in these two types of cancer. These common genes considerably participated in key pathways including the cell cycle, p۵۳ signaling pathway, progesterone-mediated oocyte maturation, and chemical carcinogenesis. Further analysis identified the AURKA gene as a pivotal druggable hub gene in both cancers. This gene encodes a cell cycle-regulated kinase protein known to exert an oncogenic influence in various malignancies, including bladder (BLCA) and breast (BRCA) cancers . Existing research also has highlighted its potential role in conferring drug resistance in cancer cells. Encouragingly, several inhibitors targeting AURKA have been developed, such as MLN۸۲۳۷ and ENMD-۲۰۷۶ demonstrating clinical efficacy in trials . Conclusion: Our computational analysis uncovered AURKA as a promising therapeutic target for managing Vulvovaginal melanoma and potentially improving its survival rates.

کلیدواژه ها:

Melanoma ، Neoplasm ، Vulvar ، Vaginal