Over-Expression of GATA3 in Large B-Cell Lymphoma Predicts Better Prognosis

Objective: The over-expression of GATA binding protein 3 (GATA3) in peripheral T-cell lymphoma is an unfavorable biomaker of patients. Given that the GATA3 is a master regulator of T cell development, the prognosis of over-expression of GATA3 in B-cell lymphoma remains unknown.

Method: The clinical features, as well as RNA sequencing data, were analyzed in six hundred and ninety-four patients with newly diagnosed LBCL (including diffuse large B-cell lymphoma, T-cell/histocyte rich LBCL, and EBV+ LBCL). Genetic aberrations, gene set enrichment analysis, and tumor immunophenotyping were compared according to GATA3 expression in RNA sequencing data. Single-cell transcriptomes from tumor samples of thirteen newly diagnosed LBCL were profiled to analyze the proportion and function of infiltrating T cells.

Results: Six hundred and ninety-four newly diagnosed LBCL patients with available bulk RNA sequence data were classified into the GATA3 high group (n = 347) and GATA3 low group (n = 347), according to the median mRNA expression level of GATA3 in lymphoma sample. Firstly, we found that the expression levels of genes involved in T cell development such as TCF7, TCF3, IKZF1 and BCL11B, and genes of T cell surface markers such as CD3E, CD4, CD8A, CD8B and CCR7 were relatively higher in GATA3 high group. Besides, GO and KEGG analysis results showed that several T cell activation, differentiation and proliferation related pathways and interferon related signaling were significantly enriched in GATA3 high group. Furthermore, ssGSEA and Cibersort TME analysis showed that CD4+ T cell subsets (Th1, Th2, Th17, Treg and Tfh) and CD8+ T cell subsets (central memory and effector memory) were significantly increased in GATA3 high group compared to GATA3 low group. The proportions of these infiltrating T cells were positively correlated with the expression of GATA3. These results showed that higher expression of GATA3 was a good indicator for more tumor infiltrating T cell in the TME of LBCL. Therefore, LBCL patients in GATA3 high group presented a remarkable prolonged 5‐year overall survival as compared to those in GATA3 low group. We also profiled single-cell transcriptomes from tumor samples of 13 newly diagnosed LBCL patients. These patients were divided into two groups, GATA3 high group (n = 8) and GATA3 low group (n = 5) based on the median mRNA expression level in RNA sequence data. The results revealed that GATA3 was mainly expressed in tumor infiltrating T-cells, but not malignant B-cells. Constant with RNA sequencing analysis, the proportion of T-cell in the TME was higher in GATA3 high group, especially the proportion of Tfh cells. We also found that the ability of antigen processing and presentation of malignant B cells in GATA3 high group were enhanced than those in GATA3 low group. Analysis of crosstalk among tumor and tumor-infiltrating cells suggested that MHC-II signaling was strengthened in GATA3 high group.

Conclusions: These data suggested that over-expression of GATA3 is a predictor for more tumor infiltrating T cells in LBCL microenvironment and favorable prognosis of patients.

No relevant conflicts of interest to declare.