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Bladder urothelial carcinoma (BLCA) accounts for 95% of all cases of bladder cancer worldwide, with a high incidence and poor prognosis. Chromobox (CBX) proteins play a key role in numerous malignant tumors; however, the role of CBX in BLCA remains unknown. Herein, the present study found that, compared with in normal bladder tissues, the expression levels of CBX1, CBX2, CBX3, CBX4 and CBX8 were markedly increased in BLCA tissues, as determined by Tumor Immune Estimation Resource, UALCAN and ONCOMINE analyses, whereas CBX6 and CBX7 were decreased in BLCA tissues. Furthermore, evident hypomethylation in the promoters of CBX1, and CBX2, as well as significant hypermethylation in the promoters of CBX5, CBX6 and CBX7, was detected in BLCA tissues compared with in normal bladder tissues. The expression of CBX1, CBX2 and CBX7 was involved in the prognosis of patients with BLCA. Low CBX7 expression was strongly associated with poorer overall survival in patients with BLCA, whereas high CBX1 and CBX2 expression was associated with poorer progression-free survival. Besides, significant associations were determined between the expression of CBXs and immune cell infiltration, including dendritic cells, neutrophils, macrophages, CD4+ T cells, CD8+ T cells and B cells. Overall, the current results may provide a rationale for developing new targets and prognostic markers for BLCA therapy. [ABSTRACT FROM AUTHOR]