CD47 as a prognostic biomarker and potential immunotherapy target in penile squamous cell carcinoma

Penile squamous cell carcinoma (PSCC) remains a global healthcare concern, characterized by poor outcomes and limited therapeutic options. CD47, a “don’t-eat-me” signal that enables tumor immune evasion, has not been extensively evaluated in PSCC. This study aims to explore the expression and significance of CD47 in PSCC. RNA-sequencing was performed on eight paired PSCC and adjacent normal tissues. Protein expression was assessed by immunohistochemistry (IHC) in an independent of 131 PSCC cases, and associations with clinicopathological factors and prognosis was evaluated. In addition, the interrogation of CD47-interacting proteins, immune cell infiltration, and signaling pathways related to CD47 subgroups were analyzed from the public database. CD47 mRNA levels were higher in PSCC tumors compared to normal tissues. High CD47 protein expression (41.98%, 55/131) significantly correlated with advanced tumor stage (P = 0.002) and larger tumor size (P = 0.002). With a median follow-up of 38 months, Kaplan-Meier survival analysis demonstrated that patients with high CD47 expression had significantly poorer overall survival (OS) (P = 0.006). Multivariate Cox regression analysis confirmed that high CD47 expression remained an independent predictor of poor OS (HR = 9.956, 95% CI 2.410–41.141, P = 0.001). Functional enrichment analyses of CD47-interacting proteins indicated involvement in immune-related and adhesion-associated pathways. Furthermore, immune infiltration analyses using CIBERSORT and IHC revealed that high CD47 expression was associated with reduced CD8 + T-cell infiltration. Gene set variation and enrichment analyses suggested activation of MYC targets and mTORC1 signaling in the high-CD47 group, which was further validated by increased phosphorylated S6K1 expression observed through IHC. These findings provide novel evidence that CD47 may serve as a promising prognostic biomarker and a potential immunotherapeutic target for PSCC.