Single-Cell and Spatial Transcriptomic Profiling of Penile Squamous Cell Carcinoma Reveals Dynamics of Tumor Differentiation and Immune Microenvironment.

ABSTRACT: Penile squamous cell carcinoma (PSCC) is a highly aggressive malignancy without effective treatment due to limited knowledge of its development and tumor microenvironment (TME). In this study, single-nucleus RNA sequencing (snRNA-seq) and high-resolution spatial transcriptomics are employed to comprehensively investigate the development trajectories and the TME. The results revealed that PSCC cells mimicked the differentiation and tissue organization of normal penile epithelium, independent of the human papillomavirus (HPV) infection status. Notably, a spatial subtype, Tum_1, appeared at early stage of tumor differentiation and in tumor-normal boundary regions. This subtype exhibited enhanced basal-like and stemness features and showed high LAMC2 expression, which activated laminin-integri

SUBMITTER: Song H 

PROVIDER: S-EPMC12412502 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature