Abstract
Extramammary Paget's disease (EMPD) is a rare cutaneous malignancy characterized by its uncertain etiology and metastatic potential. Surgery remains the first-line clinical treatment for EMPD, but the efficacy of radiotherapy and chemotherapy remains to be fully evaluated, and new therapies for EMPD are urgently needed. In this study, we initially screened 815 EMPD patients in the Surveillance, Epidemiology, and End Results (SEER) database and analyzed their clinical features and prognostic factors. Using the dataset from the Genome Sequence Archive (GSA) database, we subsequently conducted weighted gene coexpression network analysis (WGCNA), gene set enrichment analysis (GSEA), gene set variation analysis (GSVA), and immune infiltration analyses, grouping the samples based on EMPD disease status and the levels of ERBB2 expression. The prognostic analysis based on the SEER database identified increased age at diagnosis, distant metastasis, and receipt of radiotherapy as independent risk factors for EMPD. Moreover, our results indicated that patients who received chemotherapy had worse prognoses than those who did not, highlighting the urgent need for novel treatment approaches for EMPD. Functional analysis of the GSA-derived dataset revealed that EMPD tissues were significantly enriched in immune-related pathways compared with normal skin tissues. Compared with those with high ERBB2 expression, tissues with low ERBB2 expression displayed greater immunogenicity and enrichment of immune pathways, particularly those related to B cells. These findings suggest that patients with low ERBB2 expression are likely to benefit from immunotherapy, especially B-cell-related immunotherapy.