Expression of N⁶-methyladenosine (m⁶A) regulators correlates with immune microenvironment characteristics and...

This study conducted a comprehensive analysis of the clinical significance of N⁶-methyladenosine (m⁶A) regulators and their relationship with immune microenvironment characteristics in diffuse large cell lymphoma (DLBCL). Consensus clustering was performed to molecularly discriminate DLBCL subtypesbased on m⁶A regulators' expression. Using the Cox and Lasso regression algorithm, survival-associated m⁶A regulators were identified, and a m⁶A-based prognostic signature was established. The influence of m⁶A risk on immune cell infiltration, immune checkpoint genes, cancer immunity cycle, and immunotherapeutic response was evaluated. Potential molecular pathways related to m⁶A risk were investigated using gene set enrichment analysis. The m⁶A regulators showed satisfactory performance in distinguishing DLBCL subgroups with distinct clinical traits and outcomes. A six m⁶A regulator-based prognostic signature was established and validated as an independent predictor, which separated patients into low- and high-risk groups. High-risk m⁶A indicated worse survival. The B cells naïve, T cells gamma delta, and NK cells resting were the three most affected immune cells by m⁶A risk. Up-regulated (PDCD1 and KIR3DL1) and down-regulated (TIGIT, IDO1, and BTLA) immune checkpoint genes in the high-risk group were identified. The m⁶A risk was found to influence several steps in the cancer immunity cycle. Patients with high-risk m⁶A were more likely to benefit from immunotherapy. Biological function enrichment analysis revealed that high-risk m⁶A to be tended related to malignant tumor characteristics, while low-risk m⁶A showed trend to be related to defensive response processes. Collectively, the m⁶A-based prognostic signature could be a practical prognostic predictor for DLBCL and immune microenvironment characteristics affected by m⁶A may be part of the mechanism.