Identification of the Prognostic Biomarkers CBX6 and CBX7 in Bladder Cancer

Abstract

Background: Chromobox (CBX) proteins are essential components of polycomb group proteins and perform essential functions in bladder cancer (BLCA). However, research on CBX proteins is still limited, and the function of CBXs in BLCA has not been well illustrated. Methods and Results: We analyzed the expression of CBX family members in BLCA patients from The Cancer Genome Atlas database. By Cox regression analysis and survival analysis, CBX6 and CBX7 were identified as potential prognostic factors. Subsequently, we identified genes associated with CBX6/7 and performed enrichment analysis, and they were enriched in urothelial carcinoma and transitional carcinoma. Mutation rates of TP53 and TTN correlate with expression of CBX6/7. In addition, differential analysis indicated that the roles played by CBX6 and CBX7 may be related to immune checkpoints. The CIBERSORT algorithm was used to screen out immune cells that play a role in the prognosis of bladder cancer patients. Multiplex immunohistochemistry staining confirmed a negative correlation between CBX6 and M1 macrophages, as well as a consistent alteration in CBX6 and regulatory T cells (Tregs), a positive correlation between CBX7 and resting mast cells, and a negative correlation between CBX7 and M0 macrophages. Conclusions: CBX6 and CBX7 expression levels may assist in predicting the prognosis of BLCA patients. CBX6 may contribute to a poor prognosis in patients by inhibiting M1 polarization and promoting Treg recruitment in the tumor microenvironment, while CBX7 may contribute to a better prognosis in patients by increasing resting mast cell numbers and decreasing macrophage M0 content.

A robust six-gene prognostic signature based on two prognostic subtypes constructed by chromatin regulators is correlated with immunological features and therapeutic response in lung adenocarcinoma

“…Among these 27 prognostic DECRs, 23 risk and 4 protective CRs were identified. At present, many of these 27 prognostic CRs we identified have been shown to have correlations with prognosis in some cancers [48][49][50][51][52].…”

“…Among these 27 prognostic DECRs, 23 risk and 4 protective CRs were identified. At present, many of these 27 prognostic CRs we identified have been shown to have correlations with prognosis in some cancers [ 48 – 52 ]. For example, CBX6 and CBX7 were identified as prognostic biomarkers in bladder cancer [ 48 ].…”

“…At present, many of these 27 prognostic CRs we identified have been shown to have correlations with prognosis in some cancers [ 48 – 52 ]. For example, CBX6 and CBX7 were identified as prognostic biomarkers in bladder cancer [ 48 ]. PBK was found to be associated with glioblastoma and oral squamous cell carcinoma treated with radiotherapy [ 49 , 50 ].…”

Identification and validation of prognostic signature genes of bladder cancer by integrating methylation and transcriptomic analysis

“…Previously performed studies only considered a particular criteria for instance expression data, gene-specific approach, etc. to propose biomarkers 65 , 66 . Some research work proposed signature models with good performance but they all followed a different approach to create such gene sets and did not consider hallmark pathways along with other gentic fators 67 , 68 .…”

The predictive significance of chromobox family members in prostate cancer in humans

“…Several research studies have indicated that, apart from tumor genetics, the abnormal regulation of epigenetics also has a crucial impact on the progression of PCa. Although the exact roles of CBXs in PCa are still not completely understood, previous studies have indicated that CBXs, which are essential constituents of epigenetic regulatory complexes, play signi cant roles in the advancement and growth of different types of cancer [16][17][18][19][20][21].This study involved a comprehensive examination of their expression patterns and explored their associations with clinical features, prognostic importance, in ltration of immune cells, and potential functions in PCa. By employing bioinformatics, we have created a prognostic model that incorporates CBX2 and demonstrates exceptional predictive precision.…”