Longitudinal integrated spatial transcriptomic analysis of primary extramammary Paget’s disease

Background: Extramammary Paget’s disease (EMPD), a rare skin condition affecting inguinal and genital areas, has unclear cellular origins and is hard to diagnosis early due to benign-looking skin lesions.
Objectives: In this study, we sought to examine the RNA expression profiles of EMPD tissue samples to gain further insights into the disease.
Methods: Skin biopsies from a 63-year-old male with EMPD were taken at baseline to one-year post-treatment with topical imiquimod and ingenol mebutate. Histological analysis showed dermal invasion after one year. In situ RNA hybridization categorized 31 regions into normal, non-invasive and invasive EMPD, with 16 additional areas assessed for dermal inflammation.
Results: EMPD showed mTOR overactivation and unique gene expressions associated with sweat gland cells. SPDEF (SAM Pointed Domain Containing ETS Transcription Factor) was identified as a potential biomarker. Invasive EMPD differed in transcription factors from non-invasive EMPD, with gene ontology showing a shift towards epithelial-mesenchymal transition and reactive oxygen species pathways.
Limitations: The study’s reliance on in situ RNA hybridization and spatial transcriptomics may limit detection of low-abundance transcripts.
Conclusion: Utilizing spatial transcriptomics, this study identified distinct gene expression patterns and immune responses in EMPD samples, highlighting the involvement of the mTOR pathway, and transcription factors.