A cancer-associated fibroblast subtypes-based signature enables the evaluation of immunotherapy response and prognosis in bladder cancer

Yiming Qin; Xiongbing Zu; Yin Li; Ying Han; Jun Tan; Changjing Cai; Edward Shen; Ping Liu; Ganlu Deng; Ziyang Feng; Wantao Wu; Yinghui Peng; Yongting Liu; Jiayao Ma; Shan Zeng; Yihong Chen; Hong Shen

doi:10.1016/j.isci.2023.107722

A cancer-associated fibroblast subtypes-based signature enables the evaluation of immunotherapy response and prognosis in bladder cancer

iScience. 2023 Aug 25;26(9):107722. doi: 10.1016/j.isci.2023.107722. eCollection 2023 Sep 15.

Authors

Yiming Qin¹, Xiongbing Zu², Yin Li³, Ying Han³, Jun Tan⁴, Changjing Cai³, Edward Shen⁵, Ping Liu³, Ganlu Deng⁶, Ziyang Feng³, Wantao Wu³, Yinghui Peng³, Yongting Liu³, Jiayao Ma³, Shan Zeng^{3

2}, Yihong Chen³, Hong Shen^{3

2}

Affiliations

¹ Department of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.
² National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.
³ Department of Oncology, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.
⁴ Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.
⁵ Department of Life Science, McMaster University, Hamilton L8S 4L8, ON, Canada.
⁶ Department of Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530022, Guangxi, China.

Abstract

Bladder cancer (BLCA) is one of the most prevalent and heterogeneous urinary malignant tumors. Previous researches have reported a significant association between cancer-associated fibroblasts (CAFs) and poor prognosis of tumor patients. However, uncertainty surrounds the role of CAFs in the BLCA tumor microenvironment, necessitating further investigation into the CAFs-related gene signatures in BLCA. In this study, we identified three CAF subtypes in BLCA according to single-cell RNA-seq data and constructed CAFs-related risk score (CRRS) by screening 102,714 signatures. The survival analysis, ROC curves, and nomogram suggested that CRRS was a valuable predictor in 2,042 patients from 9 available public datasets and Xiangya real-world cohort. We further revealed the significant correlation between CRRS and clinicopathological characteristics, genome alterations, and epithelial-mesenchymal transition (EMT). A high CRRS indicated a non-inflamed phenotype and a lower remission rate of immunotherapy in BLCA. In conclusion, the CRRS had the potential to predict the prognosis and immunotherapy response of BLCA patients.

Keywords: Cancer; Oncology; Transcriptomics.