2. Academic Validation
  3. Single-cell and spatial transcriptomics reveal pre-metastatic subsets and therapeutic targets in penile carcinoma

Single-cell and spatial transcriptomics reveal pre-metastatic subsets and therapeutic targets in penile carcinoma

  • iScience. 2025 Jan 7;28(2):111765. doi: 10.1016/j.isci.2025.111765.
Da-Ming Xu 1 2,  Ling-Xiao Chen 3,  Hui Han 1 2,  Miao Mo 3
Affiliations

Affiliations

  • 1 State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, P.R. China.
  • 2 Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou 510060, P.R. China.
  • 3 Department of Urology, Xiangya Hospital, Central South University, Changsha 410008, P.R. China.
PMID: 39925432 DOI: 10.1016/j.isci.2025.111765
Abstract

Tumor heterogeneity, driven by branching evolution and genomic mutations, complicates Cancer treatment. Understanding malignant cell evolution across various tumors aids in identifying pre-metastatic subpopulations for optimized therapies. Using bulk RNA Sequencing (6 primary penile carcinomas, 6 metastatic lymph nodes, GSE196978), single-cell RNA Sequencing (4 advanced penile carcinomas), spatial transcriptomics (Squamous cell carcinoma [SCC]: GSE144239-GSM4565823 and SCC: GSE144239-GSM4565826), and cell assays with Silmitasertib, we mapped heterogeneity and pinpointed therapeutic targets. In penile carcinoma, we discovered an MMP3+SPP1+ pre-metastatic subset and Casein Kinase 2 alpha 1 (CK2α) overexpression. The nuclear factor κB (NF-κB) pathway may drive metastasis. Pan-cancer analysis showed that MMP3 and SPP1 link to epithelial mesenchymal transition (EMT) and drug resistance, while CK2α activates oncogenes. Silmitasertib, a CK2α inhibitor, exhibited anti-tumor effects in penile carcinoma cells. Validated across 98 single-cell and 6 spatial datasets, our study advances the understanding of tumorigenesis and metastasis, highlighting Silmitasertib as a potential therapeutic agent.

Keywords

Cancer; Omics; Transcriptomics.

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