Dysregulation of B7 family and its association with tumor microenvironment in uveal melanoma

Abstract

BackgroundUveal melanoma (UVM) is the most common primary intraocular malignancy in adults with a poor prognosis. B7 family is an important modulator of the immune response. However, its dysregulation and underlying molecular mechanism in UVM still remains unclear.MethodsData were derived from TCGA and GEO databases. The prognosis was analyzed by Kaplan-Meier curve. The ESTIMATE algorithm, CIBERSORT algorithm, and TIMER database were used to demonstrate the correlation between B7 family and tumor immune microenvironment in UVM. Single-cell RNA sequencing was used to detect the expression levels of the B7 family in different cell types of UVM. UVM was classified into different types by consistent clustering. Enrichment analysis revealed downstream signaling pathways of the B7 family. The interaction between different cell types was visualized by cell chat.ResultsThe expression level of B7 family in UVM was significantly dysregulated and negatively correlated with methylation level. The expression of B7 family was associated with prognosis and immune infiltration, and B7 family plays an important role in the tumor microenvironment (TME). B7 family members were highly expressed in monocytes/macrophages of UVM compared with other cell types. Immune response and visual perception were the main functions affected by B7 family. The result of cell chat showed that the interaction between photoreceptor cells and immune-related cells was mainly generated by HLA-C-CD8A. CABP4, KCNJ10 and RORB had the strongest correlation with HLA-C-CD8A, and their high expression was significantly correlated with poor prognosis. CABP4 and RORB were specifically expressed in photoreceptor cells.ConclusionsDysregulation of the B7 family in UVM is associated with poor prognosis and affects the tumor immune microenvironment. CABP4 and RORB can serve as potential therapeutic targets for UVM, which can be regulated by the B7 family to affect the visual perception and immune response function of the eye, thus influencing the prognosis of UVM.

The potential prognostic and immunological roles of N7-methylguanosine (m7G) in uveal melanoma

“…In recent years, numerous studies have demonstrated the crucial role of TIM in cancer progression and treatment outcomes [42][43][44]. Through GO/KEGG enrichment and correlation analysis, we found that m7G regulators are closely related to monocyte/macrophage system in the TIM, and subsequent single-cell analysis also con rmed this nding.…”

Recent Advances in Molecular and Genetic Research on Uveal Melanoma

“…Furthermore, the interaction between UM tumor cells and CD8 + T-cells has been associated with poor prognostics and was stronger in BAP1 -mutant cells using the activation of ITGB2 (integrin subunit beta 2) and ICAM1 (intercellular adhesion molecule 1) [ 224 ]. Additional aspects, such as inflammatory pathways and alterations in B7 family expression, a group of cell surface proteins that plays a critical role in the regulation of immune responses, have been correlated with diverse characteristics in UM, including cytotoxic T-cell levels and methylation patterns [ 185 , 225 ]. Interestingly, STEAP1 (six transmembrane epithelial antigen of the prostate 1) exhibits high expression levels in various types of cancers, including bladder, colon, ovarian and prostate, playing a significant role in enhancing the invasive capabilities of tumor cells [ 226 ].…”