Identification and validation of BATF as a prognostic biomarker and regulator of immune cell infiltration in acute myeloid leukemia.

BACKGROUND

Basic leucine zipper ATF-like transcription factor (BATF) is a nuclear basic leucine zipper protein affiliated with the AP-1/ATF superfamily. Previous research has confirmed that BATF expression plays a significant role in the tumour microenvironment. However, the associations between BATF expression and prognoses in acute myeloid leukaemia (AML) patients and their immunological effects remain unclear.

METHODS

Genomic and clinical AML data were got from the TCGA (TCGA-LAML) and GEO (GSE37642) databases for the subsequent analysis. The expression levels of BATF in AML patients were assessed using GEPIA, and the results were verified by qRT-PCR and Western blotting. In the meantime, the prognostic value of BATF was evaluated using univariate and multivariate analyses, receiver operating characteristic (ROC) curve (AUC) analysis, and Kaplan-Meier (KM) survival analysis. EdU, colony formation, and CCK-8 assays were employed to evaluate the proliferation of cells. Moreover, we detected the association of BATF expression with drug sensitivity through database analysis and experiments. To further investigate the mechanism of action of BATF in AML, RNA sequencing (RNA-seq) analysis was performed, followed by pathway enrichment analysis using Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Meanwhile, we detected the connection between BATF expression and the proportions of immune cells via flow cytometry in C1498 mouse model of AML. Finally, we investigated the association between BATF expression and cell-cell communication within the AML cell population using single-cell sequencing.

RESULTS

In this study, we thoroughly investigated the role of BATF in AML. First, we observed a significant elevation in the expression of BATF in patients and cells in AML. Further analysis revealed an association between high BATF expression and poor prognosis in AML. Additionally, BATF expression was found to promote the proliferative capacity of AML cells. Moreover, the results showed that the expression level of BATF dramatically affected the effect of chemotherapy in AML patients. We also discovered that BATF expression could activate multiple immune-related pathways, altering the proportions of CD8T cells and NK cells, suggesting that BATF may be a regulator of immune cell infiltration. Finally, there were differences in receptor ligand pairs between AML cells with high and low expression of BATF and immune cells.

CONCLUSION

Bioinformatics analysis and experimental verification revealed that BATF expression could alter the proportions of CD8T cells and NK cells in AML and affect drug sensitivity, making it a potential treatment target for AML.