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The roof plate-specific spondin (RSPO) family of proteins has critical roles in the tumorigenesis and progression of several carcinomas; however, little is known about their functions in bladder cancer (BLCA). This study aimed to investigate RSPO in terms of their expression levels, prognostic value, and potential mechanisms of action in BLCA. mRNA expression profiles and clinical information of BLCA patients were collected from The Cancer Genome Atlas database. Genetic alteration and DNA methylation data were obtained from cBioPortal