PROGNOSTIC SIGNIFICANCE OF KAT2A AS A HISTONE ACETYLATION REGULATOR IN DIFFUSE LARGE B‐CELL LYMPHOMA

Abstract

Diffuse large B-cell lymphoma (DLBCL) is a highly heterogeneous lymphoid neoplasm with variations in the expression of genes and genetic alterations. Histone acetylation is one of the epigenetic alterations associated with lymphoma pathogenesis. Among the many types of cell death, ferroptosis has distinct properties and has been found to be associated with physical conditions as well as various cancers. Using consensus clustering, we categorized DLBCL patients based on histone acetylation regulators and ferroptosis-related genes (HFGs) expression. LASSO Cox regression was used to calculate risk scores. Kaplan-Meier survival analysis, univariate and multivariate Cox regression analysis, and ROC curve analysis were performed. qRT-PCR was used to validate the expression of four HFGs in DLBCL cell lines. According to the study, CREBBP had the highest mutation frequency. Based on CREBBP mutations, patients were divided into mutant and wild groups, and several histone acetylation regulators were overexpressed in the mutant group. To demonstrate the potential malignant mechanisms of HFGs in DLBCL development and their prognostic value. A significant positive self-correlation was observed in HAGs and FRGs. A negative correlation was found between KAT2A, the HA writer, and the majority of FRGs (Fig. 1A). 36 genes were selected (p < 0.05) by univariate regression correlations with clinical prognosis. Consensus clustering was used to categorize the expression of DLBCL patients. K-M survival analysis showed that HFcluster B had a worse prognosis. Based on HFGs, we developed a high-quality and high-accuracy gene signature prediction model. Following LASSO Cox regression, a four-gene signature model was identified. Patients with DLBCL in the high-risk group had a significantly shorter OS (p < 0.001, Figure 1B). ROC curves, univariate and multivariate Cox regression analyses also revealed that riskScore served as an independent indicator for patients with DLBCL (p < 0.001). Analyses revealed that molecular mechanisms mediate histone acetylation and ferroptosis. The results of PCR in CD19+ B cells and DLBCL cell lines also confirmed the accuracy of the model. Due to its close relationship to ferroptosis-related genes, KAT2A was explored in greater depth. Further study revealed that KAT2A was significantly correlated with age (p = 0.028) and IPI (p = 0.016). In univariate analysis, KAT2A was an independent indicator of DLBCL patients (p < 0.001). The expression level of KAT2A was negatively correlated with OS in DLBCL patients (p = 0.003). Keywords: aggressive B-cell non-Hodgkin lymphoma, diagnostic and prognostic biomarkers No conflicts of interests pertinent to the abstract.