Identification of a risk model for prognostic and therapeutic prediction in bladder urothelial carcinoma based on infiltrating CD8+ T cells

Ligang Ma; Ruixin Li; Junjie Su; Qiong Cao; Haojie Wang; Zhihao Wei; Chengliang Wang; Chengdong Zhang; Guanyu Li; Wang Qin; Zheng Zhang; Chu Wang; Yingao Zhu; Jingjing Zhao; Shiyong Xin; Jun Ma

doi:10.1016/j.adcanc.2025.100147

Advances in Cancer Biology - Metastasis (Dec 2025)

Identification of a risk model for prognostic and therapeutic prediction in bladder urothelial carcinoma based on infiltrating CD8+ T cells

Ligang Ma,
Ruixin Li,
Junjie Su,
Qiong Cao,
Haojie Wang,
Zhihao Wei,
Chengliang Wang,
Chengdong Zhang,
Guanyu Li,
Wang Qin,
Zheng Zhang,
Chu Wang,
Yingao Zhu,
Jingjing Zhao,
Shiyong Xin,
Jun Ma

Affiliations

Ligang Ma: Department of Anesthesiology, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, 471003, China; Department of Anesthesiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China
Ruixin Li: Department of Urology, The First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, 471003, China
Junjie Su: Department of Urology, The First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, 471003, China
Qiong Cao: Department of Pathology, The Third Affiliated Hospital of Henan University of Science and Technology, 471003, China
Haojie Wang: Department of Central Laboratory, Zhengzhou University, Luoyang Central Hospital, Luoyang, 471003, China
Zhihao Wei: Department of Pathology, The Yiluo Hospital of Luoyang, The Teaching Hospital of Henan University of Science and Technology, Luoyang, 471023, China
Chengliang Wang: Department of Urology, Shangcheng County People's Hospital, Xinyang, 464000, China
Chengdong Zhang: Department of Urology, Xinxiang First People's Hospital, Xinxiang, 453000, China
Guanyu Li: Department of Urology, The First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, 471003, China
Wang Qin: Department of Urology, The First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, 471003, China
Zheng Zhang: Department of Urology, The First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, 471003, China
Chu Wang: Department of Urology, The First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, 471003, China
Yingao Zhu: Department of Urology, The First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, 471003, China
Jingjing Zhao: Department of Anesthesiology, The Third Affiliated Hospital of Henan University of Science and Technology, Luoyang, 471003, China
Shiyong Xin: Department of Urology, The First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, 471003, China; Corresponding author. Department of Urology, The First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, No.636, Guan-lin Road, Luo-Long District, Luoyang, 471000, China.
Jun Ma: Department of Anesthesiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China; Corresponding author. No. 2 Anzhen Road, Chaoyang District, Beijing, 100029, China.

DOI: https://doi.org/10.1016/j.adcanc.2025.100147
Journal volume & issue: Vol. 15
p. 100147

Abstract

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Background: With increasing evidence indicating that immune cells significantly contribute to tumor progression, elucidating their role in tumor prognosis and therapy has become imperative. This study aims to thoroughly characterize tumor-infiltrating immune cells in bladder cancer (BLCA) and identify key immune cells and gene models associated with prognosis and therapeutic outcomes in BLCA. Methods: Initially, we assessed the relationship between the abundance of infiltrating immune cells and prognosis, CD8+T cell was selected to establish the risk model, which was constructed based on five key genes. Then ROC curve was drawn to demonstrate the risk model had high prognosis predictive value in BLCA. Results: Our correlation analysis revealed that riskscore was negatively associated with several steps of the tumor immune cycle. Additionally, the risk score exhibited a negative correlation with the expression levels of CD8,CD274,IFNG, Merck18, and several common immune checkpoints. Furthermore, the tumor exclusion score and Tumor Immune Dysfunction and Exclusion (TIDE) score were significantly higher in the high-score group compared to the low-score group. Notably, the risk score demonstrated a negative correlation with the enrichment score of immunotherapy-related pathways, indicating that the therapeutic benefit was greater in the low-score group than in the high-score group. Then, a total of 171 chemotherapy and targeted drugs were identified. Subsequently, immunohistochemistry, EDU and Western blot were used to verify our result. Conclusions: Our results confirmed that the tumor infiltration CD8+ T cells in tumors plays a critical role in the prognosis and treatment of bladder cancer (BLCA). This insight may offer new directions and inspiration for prognostic prediction and therapeutic strategies for bladder cancer in the future.

Published in Advances in Cancer Biology - Metastasis

ISSN: 2667-3940 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: https://www.journals.elsevier.com/advances-in-cancer-biology-metastasis

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