GATA2 as an outcome signature: promoting bladder cancer migration and inhibiting PD-L1 expression

Abstract:

Background: Embryonic development is regulated by stem cells, and epithelial-to-mesenchymal transition (EMT) is associated with cell stemness ; nevertheless, the EMT regulation by embryonic development-related genes has not been studied. Immune checkpoints exert an essential effect in tumor treatment ; however, their regulatory mechanisms have not been fully elucidated.

Methods: We obtained clinicopathological and transcriptome data from The Cancer Genome Atlas. Embryonic development- associated genes were obtained from The Human Gene Database. We identified genes using univariate Cox regression analysis and identified various subtypes using consensus clustering analysis. Immunoassays were performed using the CIBERSORT package and Estimation of Stromal and Immune cells in the Malignant Tumor tissues using an expression data algorithm. The least absolute shrinkage and selection operator algorithm and multivariate Cox regression analysis were adopted to generate the prognostic model. We used the OCLR and TIDE algorithms. We conducted functional experiments.

Results: wenty-two embryonic development-associated genes were risk factors for bladder cancer, and their expression levels significantly correlated with the TNM stage. We assessed the extent of immune infiltration, regulation of immune checkpoints, and responses to immune checkpoint blockade based on these genes. These risk genes were associated with EMT and modulated immune checkpoints. Cellular experiments demonstrated that EVC2 and GATA2 drive BLCA invasion and migration. GATA2 regulated the PD-L1 expression.

Conclusion: We identified three critical genes: RUNX2, GATA2 and EVC2. These three genes are related to EMT and immune cell infiltration and are independent prognostic elements for BLCA.