Cytoskeleton regulator RNA expression on cancer-associated fibroblasts is associated with prognosis and immunotherapy response in bladder cancer
Yucai Wu,
Yangyang Xu,
Shiming He,
Yifan Li,
Ninghan Feng,
Jian Fan,
Yanqing Gong,
Xuesong Li,
Liqun Zhou
Affiliations
Yucai Wu
Department of Urology, Peking University First Hospital, Beijing, China; Institute of Urology, Peking University, Beijing, China; National Urological Cancer Center, Beijing, China; Urogenital Diseases (Male) Molecular Diagnosis and Treatment Center, Peking University, Beijing, China
Yangyang Xu
Department of Urology, Peking University First Hospital, Beijing, China; Institute of Urology, Peking University, Beijing, China; National Urological Cancer Center, Beijing, China; Urogenital Diseases (Male) Molecular Diagnosis and Treatment Center, Peking University, Beijing, China
Shiming He
Department of Urology, Peking University First Hospital, Beijing, China; Institute of Urology, Peking University, Beijing, China; National Urological Cancer Center, Beijing, China; Urogenital Diseases (Male) Molecular Diagnosis and Treatment Center, Peking University, Beijing, China
Yifan Li
Department of Urology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Jiangsu, China
Department of Urology, Peking University First Hospital, Beijing, China; Institute of Urology, Peking University, Beijing, China; National Urological Cancer Center, Beijing, China; Urogenital Diseases (Male) Molecular Diagnosis and Treatment Center, Peking University, Beijing, China; Corresponding author. Department of Urology, Peking University First Hospital, NO.8, Xishiku Street, Xicheng, Beijing 100034, China.
Yanqing Gong
Department of Urology, Peking University First Hospital, Beijing, China; Institute of Urology, Peking University, Beijing, China; National Urological Cancer Center, Beijing, China; Urogenital Diseases (Male) Molecular Diagnosis and Treatment Center, Peking University, Beijing, China
Xuesong Li
Department of Urology, Peking University First Hospital, Beijing, China; Institute of Urology, Peking University, Beijing, China; National Urological Cancer Center, Beijing, China; Urogenital Diseases (Male) Molecular Diagnosis and Treatment Center, Peking University, Beijing, China; Corresponding authors. Department of Urology, Peking University First Hospital, NO.8, Xishiku Street, Xicheng, Beijing 100034, China.
Liqun Zhou
Department of Urology, Peking University First Hospital, Beijing, China; Institute of Urology, Peking University, Beijing, China; National Urological Cancer Center, Beijing, China; Urogenital Diseases (Male) Molecular Diagnosis and Treatment Center, Peking University, Beijing, China; Corresponding author. Department of Urology, Peking University First Hospital, NO.8, Xishiku Street, Xicheng, Beijing 100034, China.
Background: Dysregulation of long noncoding RNAs (lncRNAs) has been reported to be associated with multiple tumors where they act as tumor suppressors or accelerators. The lncRNA CYTOR was identified as an oncogene involved in many cancers, such as gastric cancer, colorectal cancer, hepatocellular carcinoma, and renal cell carcinoma. However, the role of CYTOR in bladder cancer (BCa) has rarely been reported. Methods: Using cancer datasets from The Cancer Genome Atlas (TCGA) program, we analyzed the association between CYTOR expression and prognostic value, oncogenic pathways, antitumor immunity and immunotherapy response in BCa. The influence of CYTOR on the immune infiltration pattern in the urothelial carcinoma microenvironment was further verified in our dataset. Single-cell analysis revealed the role of CYTOR in the tumor microenvironment (TME) of BCa. Finally, we evaluated the expression of CYTOR in BCa in the Peking University First Hospital (PKU–BCa) dataset and its correlation with the malignant phenotype of BCa in vitro and in vivo. Results: The results indicated that CYTOR was highly expressed in multiple cancer samples, including BCa, and increased CYTOR expression contributed to poor overall survival (OS). Additionally, elevated CYTOR expression was significantly correlated with clinicopathological features of BCa, such as female sex, advanced TNM stage, high histological grade and non-papillary subtype. Functional characterization revealed that CYTOR may be involved in immune-related pathways and the epithelial mesenchymal transformation (EMT) process. Moreover, CYTOR had a significant association with infiltrating immune cells, including M2 macrophages and regulatory T cells (Tregs). CYTOR facilitates the crosstalk between cancer-associated fibroblasts (CAFs) and macrophages, and mediates M2 polarization of macrophages. Correlation analysis revealed a positive correlation between CYTOR expression and programmed cell death-1 (PD-1)/programmed death ligand 1 (PD-L1)/expression and other targets for specific immunotherapy in BCa, which are recognized to predict the efficacy of immunotherapy. Conclusions: These results suggest that CYTOR serves as a potential biomarker for predicting survival outcome, TME cell infiltration characteristics and immunotherapy response in BCa.