Cytoskeleton regulator RNA expression on cancer-associated fibroblasts is associated with prognosis and immunotherapy response in bladder cancer.

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 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 in bladder cancer (BCa) has rarely been reported.

METHODS

Using cancer datasets from The Cancer Genome Atlas (TCGA) program, we analyzed the association between expression and prognostic value, oncogenic pathways, antitumor immunity and immunotherapy response in BCa. The influence of on the immune infiltration pattern in the urothelial carcinoma microenvironment was further verified in our dataset. Single-cell analysis revealed the role of in the tumor microenvironment (TME) of BCa. Finally, we evaluated the expression of in BCa in the Peking University First Hospital (PKU-BCa) dataset and its correlation with the malignant phenotype of BCa and .

RESULTS

The results indicated that was highly expressed in multiple cancer samples, including BCa, and increased expression contributed to poor overall survival (OS). Additionally, elevated 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 may be involved in immune-related pathways and the epithelial mesenchymal transformation (EMT) process. Moreover, had a significant association with infiltrating immune cells, including M2 macrophages and regulatory T cells (Tregs). facilitates the crosstalk between cancer-associated fibroblasts (CAFs) and macrophages, and mediates M2 polarization of macrophages. Correlation analysis revealed a positive correlation between expression and programmed cell death-1 ()/programmed death ligand 1 ()/expression and other targets for specific immunotherapy in BCa, which are recognized to predict the efficacy of immunotherapy.

CONCLUSIONS

These results suggest that serves as a potential biomarker for predicting survival outcome, TME cell infiltration characteristics and immunotherapy response in BCa.