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Here, we generated a comprehensive single\u2010cell map of PSCC (66\u00a0421 cells) and identified 9 distinct cell populations with samples from nine tumor samples and six adjacent normal samples. Among the malignant cells, SEMA3C\n                    <jats:sup>high<\/jats:sup>\n                    Mals was found to be associated with epithelial\u2010mesenchymal transition. T cells in tumor tissues are in a highly exhausted state, while SPP1\n                    <jats:sup>high<\/jats:sup>\n                    TAMs were observed to promote tumor progression. Cancer\u2010associated fibroblasts were found to interact with malignant cells to facilitate EMT through several pathways. Notably, there is a specific type of pericyte called POSTN\n                    <jats:sup>+<\/jats:sup>\n                    pericytes, which can promote angiogenesis and extracellular matrix remodeling in PSCC. Finally, SEMA3C was identified as an effective biomarker reflecting cancer stage and microvessel density. Overall, we investigated the heterogeneity of TME from a single\u2010cell perspective and demonstrated that SEMA3C serve as an effective biomarker for predicting lymph node metastasis and prognosis in PSCC. These findings may offer valuable insights for future therapeutic strategies.\n                  <\/jats:p>","DOI":"10.1002\/advs.202503894","type":"journal-article","created":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T19:20:58Z","timestamp":1770232858000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Decoding the Cellular Heterogeneity and Malignant Progression of Human Penile Squamous Cell Carcinoma by Single\u2010Cell RNA Sequencing"],"prefix":"10.1002","volume":"13","author":[{"given":"Xiheng","family":"Hu","sequence":"first","affiliation":[{"name":"Department of Urology Xiangya Hospital Central South University  Changsha Hunan China"},{"name":"National Engineering Research Center of Personalized Diagnostic and Therapeutic Technology Central South University  Changsha Hunan China"},{"name":"Furong Laboratory  Changsha Hunan China"},{"name":"Department of Dermatology Hunan Engineering Research Center 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