Single-Cell and Spatial Transcriptomic Profiling of Penile Squamous Cell Carcinoma Reveals Dynamics of Tumor Differentiation and Immune Microenvironment

被引：0

作者：

Song, Hongjian ^{[1
,2
,3
]}

Tong, Zhichao ^{[1
,3
,4
,5
,6
]}

Xie, Guixiang ^{[7
]}

Li, Yaowei ^{[1
,2
,3
]}

Zhao, Yubo ^{[1
,3
,8
,9
]}

Fan, Fengpu ^{[10
,11
]}

Yang, Zongzheng ^{[1
,2
,3
,10
]}

Shi, Qing ^{[1
,2
,3
]}

Zhang, Qian ^{[10
,11
]}

Wen, Feng ^{[10
]}

Meng, Hongxue ^{[12
]}

Li, Haonan ^{[1
,2
,3
]}

Guo, Pengyu ^{[1
,2
,3
]}

Hou, Dayong ^{[1
,3
,13
]}

Zhang, Zhenwei ^{[1
,2
,3
]}

Yin, Zhihao ^{[1
,2
,3
]}

Liu, Ziyi ^{[1
,2
,3
]}

Wang, Jianwei ^{[1
,2
,3
]}

Zhang, Peng ^{[1
,2
,3
]}

Dai, Peng ^{[1
,2
,3
]}

Li, Changfu ^{[2
]}

Teng, Lichen ^{[2
]}

Xu, Yangyang ^{[2
]}

Ding, Dexin ^{[2
]}

Xu, Tao ^{[2
]}

Li, Jianzhang ^{[2
]}

Chen, Yongsheng ^{[2
]}

Qiu, Yu ^{[8
]}

Hu, Xiaowei ^{[5
]}

Liu, Wentao ^{[5
]}

Wu, Liang ^{[7
]}

Nawroth, Roman ^{[6
]}

Li, Guibo ^{[7
]}

Su, Hang ^{[10
,14
]}

Deng, Ziqing ^{[10
,15
]}

Wang, Ziqi ^{[1
,2
,3
,16
,17
]}

Wang, Di ^{[1
,10
]}

Xu, Wanhai ^{[1
,2
,3
,8
]}

机构：

[1] Harbin Med Univ, Canc Hosp, Affiliated Hosp 2, NHC Key Lab Mol Probes & Targeted Theranost, Harbin 150001, Peoples R China

[2] Harbin Med Univ, Canc Hosp, Dept Urol, Harbin 150001, Peoples R China

[3] Harbin Med Univ, Canc Hosp, Heilongjiang Prov Key Lab Basic Med Sci Urol Canc, Harbin 150001, Peoples R China

[4] Harbin Med Univ, Canc Hosp, Biobank, Harbin 150001, Peoples R China

[5] Harbin Med Univ, Canc Hosp, Dept Urogenital Med Oncol, Harbin 150001, Peoples R China

[6] Tech Univ Munich, Dept Urol, Klinikum Rechts Isar, D-80333 Munich, Germany

[7] BGI Res, Chongqing 401329, Peoples R China

[8] Harbin Med Univ, Affiliated Hosp 2, Dept Urol, Harbin 150086, Heilongjiang, Peoples R China

[9] Harbin Engn Univ, Ctr Biomed Mat & Engn, Harbin 150001, Peoples R China

[10] BGI Res, Beijing 102601, Peoples R China

[11] Univ Chinese Acad Sci, Coll Life Sci, Beijing 100049, Peoples R China

[12] Harbin Med Univ, Canc Hosp, Dept Pathol, Harbin 150001, Peoples R China

[13] Harbin Med Univ, Dept Med Image Ctr, Canc Hosp, Harbin 150001, Peoples R China

[14] BGI Heilongjiang Om Hlth Axis Intelligent Lab, BGI HL OHA Intelligent Lab, Harbin 150001, Peoples R China

[15] Shanxi Med Univ, BGI Collaborat Ctr Future Med, Taiyuan 030001, Peoples R China

[16] Harbin Med Univ, Canc Hosp, Dept Cystoscope Ctr, Harbin 150001, Peoples R China

[17] Harbin Med Univ, State Key Lab Frigid Zone Cardiovasc Dis, Harbin 150001, Heilongjiang, Peoples R China

来源：

ADVANCED SCIENCE | 2025年

基金：

中国国家自然科学基金; 黑龙江省自然科学基金;

关键词：

penile squamous cell carcinoma; single-nucleus RNA sequencing; spatial landscape; spatial transcriptomics; tumor microenvironment; EXPRESSION; CANCER; HEAD; COMMUNICATION; HETEROGENEITY; INFERENCE; LAMC2; DNA;

D O I：

10.1002/advs.202500216

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Penile squamous cell carcinoma (PSCC) is a highly aggressive malignancy without effective treatment due to limited knowledge of its development and tumor microenvironment (TME). In this study, single-nucleus RNA sequencing (snRNA-seq) and high-resolution spatial transcriptomics are employed to comprehensively investigate the development trajectories and the TME. The results revealed that PSCC cells mimicked the differentiation and tissue organization of normal penile epithelium, independent of the human papillomavirus (HPV) infection status. Notably, a spatial subtype, Tum_1, appeared at early stage of tumor differentiation and in tumor-normal boundary regions. This subtype exhibited enhanced basal-like and stemness features and showed high LAMC2 expression, which activated laminin-integrin signaling via ITGA6/ITGB4, promoting tumor invasiveness. Furthermore, the results indicated that HPV-positive basal stem-like neoplasms dampened the immune function of T cells and macrophages, promoting an immunosuppressive environment that facilitates tumor progression. Supporting this, the patients with head and neck squamous cell carcinoma and lung squamous cell carcinoma who have high expression of HPV-positive Tum_1 signatures derived greater benefit from PD-1 blockade therapy. In summary, the findings provide a comprehensive spatial landscape of the PSCC TME and suggest potential treatment approaches targeting laminin-integrin interaction and immunotherapy, especially in HPV-positive patients.

引用

页数：19

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