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Integrative bioinformatics approaches to map key biological markers and therapeutic drugs in Extramammary Paget’s disease of the scrotum

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Integrative bioinformatics approaches to map key biological markers and therapeutic drugs in Extramammary Paget’s disease of the scrotum

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.

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Extramammary Paget Disease

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Extramammary Paget Disease

Extramammary Paget disease (EMPD) is a rare dermatologic condition that frequently presents in areas where apocrine sweat glands are abundant, most commonly the vulva, although perineal, scrotal, perianal, and penile skin may also be affected. Lesions clinically present as erythematous, well-demarcated plaques that may become erosive, ulcerated, scaly, or eczematous. Extramammary Paget disease has a female predominance and usually occurs in the sixth to eighth decades of life. Professionals disagree about many aspects of EMPD, for example, the prevalence of concurrent vulvar adenocarcinoma or invasive EMPD, association with regional and distant cancers, and recurrence rates following surgical excision. Early recognition is imperative because the diagnosis is frequently delayed and there is a high incidence of associated invasive disease.

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Ultrastructural study of extramammary Paget's disease -- histologically showing transition from bowenoid pattern to Paget's disease pattern.

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Ultrastructural study of extramammary Paget's disease -- histologically showing transition from bowenoid pattern to Paget's disease pattern.

Histological, immunohistochemical, and ultrastructural studies were performed on two cases of histologically unusual extramammary Paget's disease. Histologically, the central area of the lesions showed a bowenoid pattern, and the peripheral area showed typical extramammary Paget's disease. The transition zone showed an intermediate pattern. All these areas were positive for CEA and EMA, and negative for S-100 protein. Ultrastructurally, in the intermediate pattern, the tumour cells had abundant cytoplasmic glycogen, and the widened intercellular spaces contained numerous glycogen particles, which were probably secreted by the tumour cells. It is well known that eccrine glands, but not apocrine glands, secrete glycogen particles. Therefore, the present findings suggest that some cases of extramammary Paget's disease are a proliferation of germinative cells with eccrine gland differentiation.

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