BAG2 Is a Novel Prognostic Biomarker and Promising Immunotherapy Target in Uveal Melanoma.

Background: The importance of BAG2 in malignancy is gradually being recognized, however, information on its role in uveal melanoma (UVM) is limited. We aimed to elucidate its function and potential mechanism of action in UVM.

Methods: Using the Cancer Genome Atlas (TCGA) and GEO-related datasets, we analyzed the differential expression of BAG2 in tumors, combined with clinical information and methylation data to analyze the prognostic value of BAG2, differential methylation and its association with UVM metastasis. In addition, correlation analysis explored the immunological characteristics of BAG2 in UVM and the response to immunotherapy. Finally, a prognostic model of ferroptosis- related genes was constructed and validated.

Results: BAG2 is significantly downregulated in multiple cancers including UVM. Prognostic analysis showed that BAG2 was an independent prognostic factor for UVM. Abnormal methylation of BAG2 may affect the metastasis of UVM and be significantly associated with poor prognosis. Immune analysis clarified that BAG2 was significantly associated with UVM immune cell infiltration and multiple immune checkpoints, and low expression of BAG2 was more beneficial in immunotherapy. In addition, the prognostic model of ferroptosis we constructed has good performance in predicting overall survival and metastasis-free survival of UVM.

Conclusions: BAG2 is an independent prognostic factor for UVM and may be a potential immune checkpoint for UVM.