Penile squamous cell carcinoma (PSCC) can affect men of any age, but we know little about the differences between non-old and old patients with PSCC, which severely limits the precise diagnosis and treatment of PSCC.
We collected 2 non-old and 3 old PSCC samples and performed single-cell RNA sequencing and single-cell TCR-Seq analysis. All samples were subjected to UMAP clustering, and subcluster analyses were carried out on tumor cells, T cells, and myeloid cells. Furthermore, cell trajectory analyses were completed for tumor cells and T cells. We performed immunohistochemistry for DCN, KITLG, GPX4, and EPCAM and immunofluorescence for CD24 and MIF, as well as Masson staining and β-galactosidase staining on tissues. Macrophages were cultured for flow cytometry to detect the expression of HLA-DR on the cell surface after MIF treatment.
We found that tumor cells in older PSCC demonstrated a more pronounced senescence-associated secretory phenotype (SASP) and gave rise to a subcluster of senescence-associated tumor cells, which exhibited stronger malignant features. Interestingly, we observed similar alterations in old head and neck squamous cell carcinoma (HNSC) samples. In addition, older PSCC samples also had more dysfunctional-like CD24 + T cells and more angiogenic macrophages. Finally, we revealed enhanced MIF signaling between fibroblasts and other cells to be another significant feature of aging PSCC.
Our study systematically addressed the effects of aging on PSCC and identified IL1B as a potential prognostic marker for PSCC, offering a framework for the classification management and treatment of PSCC patients.
Cell biology and toxicology. 2026 Jun 06 [Epub ahead of print]
Jian Cao, Lin Du, Zailong Qin, Aiwei Ma, Hao Bo, Xueheng Zhao, Yanwei Luo, Chunlin Ou, Zhizhong Liu, Yu Xie, Wancong Zhang, Shijie Tang, Yu Tian, Junbin Yuan, Zhaojian Gong, Jie Guo
Department of Urology, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University/Hunan Cancer Hospital, Changsha, 410000, Hunan, China., Department of Blood Transfusion, The Third Xiangya Hospital of Central South University, Changsha, 410000, Hunan, China., Genetic and Metabolic Central Laboratory, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Guangxi Birth Defects Research and Prevention Institute, Nanning, 530000, Guangxi, China., Department of Plastic Surgery and Burn Center, Second Affiliated Hospital, Shantou University Medical College, Shantou, 515000, China., NHC Key Laboratory of Human Stem Cell and Reproductive Engineering, School of Basic Medical Science, Central South University, Changsha, 410000, Hunan, China., Department of Pathology, Xiangya Hospital, Central South University, Changsha, 410000, Hunan, China., Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, 410000, China., Department of Urology, Xiangya Hospital, Central South University, Changsha, 410000, Hunan, China. ., Department of Oral and Maxillofacial Surgery, The Second Xiangya Hospital of Central South University, Changsha, 410000, Hunan, China. ., National Institution of Drug Clinical Trial, Xiangya Hospital, Central South University, Changsha, 410000, China. .