Malassezia May Contribute to Basal Cell Carcinoma Development via Inflammatory and Oxidative Stress Pathways

ABSTRACT Basal cell carcinoma (BCC) is the most common malignant skin tumor. Skin‐resident lipophilic Malassezia yeasts are associated with various cutaneous disorders, while their correlative patterns and potential biological effects in BCC tissues remain insufficiently defined. We used RT‐qPCR screening of archived FFPE BCC specimens and metagenomic sequencing of three paired fresh tumor and peritumoral tissues to characterize tissue‐associated Malassezia colonization. M. globosa was the most abundant species in FFPE samples and was also detectable in fresh tissues. In vitro functional assays (CCK‐8, EdU) in HaCaT keratinocytes and A‐431 epidermoid carcinoma cells showed that 12 h stimulation with optimal concentrations of M. globosa (1.2 × 10 7 CFU/mL) and M. yamatoensis (1.6 × 10 7 CFU/mL) significantly promoted epithelial cell proliferation. Transcriptome sequencing and subsequent RT‐qPCR validation further showed that both strains significantly upregulate pro‐inflammatory genes ( IL‐1β , IL‐6 , TNF‐α ) and oxidative stress‐related genes ( SOD1, SOD2) in these cell lines. Collectively, our findings describe a correlative association between Malassezia colonization and BCC lesions and offer preliminary in vitro mechanistic clues.