DataVXAdvanced SciencePaper
journal article·2026-03Open access

Decoding the Cellular Heterogeneity and Malignant Progression of Human Penile Squamous Cell Carcinoma by Single‐Cell RNA Sequencing

Xiheng Hu, Wensheng Shi, Liang Dong, Lingjuan Huang, Xiyuan Zhang, Yiting Feng, Jie Sun, Lanlan Liu, Teng Liu, Jun Fu, Bowen Zhong, Qihao Leng, Xiaohua Wu, Minfeng Chen, Lingfang Li, Yuan Li, Xin Jin, Long Wang, Jian Cao, Xin Li, Mingzhu Yin, Xiang Chen

Advanced Science· Volume 13· Issue 14
Publisher pageOpen full text
Source abstract

Abstract

ABSTRACT Penile squamous cell carcinoma (PSCC) is a rare genitourinary malignancy, and factors of its tumor microenvironment (TME) could serve as prognostic indicators for tumor recurrence and metastasis. Here, we generated a comprehensive single‐cell map of PSCC (66 421 cells) and identified 9 distinct cell populations with samples from nine tumor samples and six adjacent normal samples. Among the malignant cells, SEMA3C high Mals was found to be associated with epithelial‐mesenchymal transition. T cells in tumor tissues are in a highly exhausted state, while SPP1 high TAMs were observed to promote tumor progression. Cancer‐associated fibroblasts were found to interact with malignant cells to facilitate EMT through several pathways. Notably, there is a specific type of pericyte called POSTN + 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‐cell 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.
Source: crossref · Quality: baseline

Research context

OpenAlex topics: Genital Health and Disease · Single-cell and spatial transcriptomics · Hippo pathway signaling and YAP/TAZ

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Urology Xiangya Hospital Central South University Changsha Hunan China

National Engineering Research Center of Personalized Diagnostic and Therapeutic Technology Central South University Changsha Hunan China

Furong Laboratory Changsha Hunan China

Department of Dermatology Hunan Engineering Research Center of Skin Health and Disease Hunan Key Laboratory of Skin Cancer and Psoriasis Xiangya Hospital Central South University Changsha Hunan China

Department of Urology the Second Xiangya Hospital Central South University Changsha China

Clinical Research Center (CRC) Medical Pathology Center (MPC) Cancer Early Detection and Treatment Center (CEDTC) and Translational Medicine Research Center (TMRC) Chongqing University Three Gorges Hospital Chongqing University Chongqing China

School of Medicine Chongqing University Chongqing China

CQU ‐ Ferenc Krausz Nobel Laureate Scientific Workstation Chongqing University Three Gorges Hospital & Academy for Advanced Interdisciplinary Technology Chongqing China

Department of Cardiovascular Medicine Xiangya Hospital Central South University Changsha China

Department of Urology The Third Xiangya Hospital of Central South University Changsha Hunan China

Department of Urology The Affiliated Cancer Hospital of Xiangya School of Medicine Central South University/Hunan Cancer Hospital Changsha China

Funding

Science Fund for Distinguished Young Scholars of Hunan Province

References (76)

Show source-provided references
1. 10.1038/s41572-021-00246-510.1038/s41572-021-00246-5 ↗
2. 10.6004/jnccn.2013.007510.6004/jnccn.2013.0075 ↗
3. 10.1517/17460441.2014.92587510.1517/17460441.2014.925875 ↗
4. 10.1200/JCO.2010.29.547710.1200/JCO.2010.29.5477 ↗
5. 10.1038/s41585-018-0083-010.1038/s41585-018-0083-0 ↗
6. 10.1038/s41585-022-00617-x10.1038/s41585-022-00617-x ↗
7. 10.1038/ni.270310.1038/ni.2703 ↗
8. 10.1038/nrc.2017.510.1038/nrc.2017.5 ↗
9. 10.3389/fimmu.2022.102492510.3389/fimmu.2022.1024925 ↗
10. 10.1038/nm.339410.1038/nm.3394 ↗
11. 10.1186/s12943-021-01428-110.1186/s12943-021-01428-1 ↗
12. 10.1016/j.cell.2015.10.03910.1016/j.cell.2015.10.039 ↗
13. 10.1016/j.eururo.2024.03.03810.1016/j.eururo.2024.03.038 ↗
14. 10.1002/advs.20250021610.1002/advs.202500216 ↗
15. 10.1126/science.aax024910.1126/science.aax0249 ↗
16. 10.1186/s13059-016-1028-710.1186/s13059-016-1028-7 ↗
17. 10.1093/nar/gky113110.1093/nar/gky1131 ↗
18. 10.1038/s41592-019-0619-010.1038/s41592-019-0619-0 ↗
19. 10.1038/s41467-020-15980-910.1038/s41467-020-15980-9 ↗
20. 10.3390/cancers1510271910.3390/cancers15102719 ↗
21. 10.1007/s13277-016-4951-z10.1007/s13277-016-4951-z ↗
22. 10.1016/j.canlet.2019.11.00910.1016/j.canlet.2019.11.009 ↗
23. 10.1038/nri97810.1038/nri978 ↗
24. 10.1016/j.cell.2021.01.01010.1016/j.cell.2021.01.010 ↗
25. 10.1016/j.ccell.2014.10.01810.1016/j.ccell.2014.10.018 ↗
26. 10.1038/s41573-018-0004-110.1038/s41573-018-0004-1 ↗
27. 10.1016/j.cell.2020.03.01310.1016/j.cell.2020.03.013 ↗
28. 10.1084/jem.2016202410.1084/jem.20162024 ↗
29. 10.1093/nar/gkt41010.1093/nar/gkt410 ↗
30. 10.1186/s12943-022-01658-x10.1186/s12943-022-01658-x ↗
31. 10.7150/ijbs.3994710.7150/ijbs.39947 ↗
32. 10.1002/cac2.1248210.1002/cac2.12482 ↗
33. 10.1038/s41467-021-21246-910.1038/s41467-021-21246-9 ↗
34. 10.1038/s41368-021-00139-z10.1038/s41368-021-00139-z ↗
35. 10.1016/j.labinv.2023.10017710.1016/j.labinv.2023.100177 ↗
36. 10.1038/s41568-018-0038-z10.1038/s41568-018-0038-z ↗
37. 10.1016/S0022-5347(05)66450-610.1016/S0022-5347(05)66450-6 ↗
38. 10.1038/s41586-024-07698-110.1038/s41586-024-07698-1 ↗
39. 10.1016/j.celrep.2021.10925310.1016/j.celrep.2021.109253 ↗
40. 10.1096/fj.01-0632fje10.1096/fj.01-0632fje ↗
41. 10.1016/j.cell.2019.10.00310.1016/j.cell.2019.10.003 ↗
42. 10.1016/j.cell.2020.03.04810.1016/j.cell.2020.03.048 ↗
43. 10.1093/jnci/94.12.88310.1093/jnci/94.12.883 ↗
44. 10.1093/nar/gky117310.1093/nar/gky1173 ↗
45. 10.1089/cmb.2017.009610.1089/cmb.2017.0096 ↗
46. 10.1093/bioinformatics/bts63510.1093/bioinformatics/bts635 ↗
47. 10.1093/bioinformatics/btt65610.1093/bioinformatics/btt656 ↗
48. 10.1016/j.cels.2018.11.00510.1016/j.cels.2018.11.005 ↗
49. 10.1089/omi.2011.011810.1089/omi.2011.0118 ↗
50. 10.1038/s41467-019-09234-610.1038/s41467-019-09234-6 ↗
51. 10.1101/gr.133991.11110.1101/gr.133991.111 ↗
52. 10.1126/science.abe647410.1126/science.abe6474 ↗
53. 10.1186/1471-2105-14-710.1186/1471-2105-14-7 ↗
54. 10.1038/nmeth.415010.1038/nmeth.4150 ↗
55. 10.1038/nbt.285910.1038/nbt.2859 ↗
56. 10.1038/s41419-018-0736-110.1038/s41419-018-0736-1 ↗
57. Overexpression of ID1 Promotes Tumor Progression in Penile Squamous Cell Carcinoma
58. 10.1016/j.urolonc.2019.04.01310.1016/j.urolonc.2019.04.013 ↗
59. 10.3390/cells203062110.3390/cells2030621 ↗
60. 10.1016/j.cmet.2013.08.00810.1016/j.cmet.2013.08.008 ↗
61. 10.1038/ki.2011.20810.1038/ki.2011.208 ↗
62. 10.1038/s41467-020-18794-x10.1038/s41467-020-18794-x ↗
63. 10.3389/fimmu.2017.0191110.3389/fimmu.2017.01911 ↗
64. 10.7150/thno.1082410.7150/thno.10824 ↗
65. 10.1002/ijc.2890610.1002/ijc.28906 ↗
66. 10.1111/j.1755-148X.2011.00929.x10.1111/j.1755-148X.2011.00929.x ↗
67. 10.3748/wjg.v21.i21.664910.3748/wjg.v21.i21.6649 ↗
68. 10.1038/s12276-022-00785-110.1038/s12276-022-00785-1 ↗
69. 10.1016/j.cub.2013.05.02310.1016/j.cub.2013.05.023 ↗
70. 10.1073/pnas.94.26.1471310.1073/pnas.94.26.14713 ↗
71. 10.1002/(SICI)1096-9098(199909)72:1<18::AID-JSO5>3.0.CO;2-P10.1002/(SICI)1096-9098(199909)72:1<18::AID-JSO5>3.0.CO;2-P ↗
72. 10.1111/cas.1200310.1111/cas.12003 ↗
73. 10.1074/jbc.M109.05512910.1074/jbc.M109.055129 ↗
74. Increased Class 3 Semaphorin Expression Modulates the Invasive and Adhesive Properties of Prostate Cancer Cells
75. 10.1016/j.yexcr.2013.02.00310.1016/j.yexcr.2013.02.003 ↗
76. 10.1186/bcr362110.1186/bcr3621 ↗