Expression of N6-methyladenosine (m6A) regulators correlates with immune microenvironment characteristics and predicts prognosis in diffuse large cell lymphoma (DLBCL)

This study conducted a comprehensive analysis of the clinical significance of N-6-methyladenosine (m(6)A) regulators and their relationship with immune microenvironment characteristics in diffuse large cell lymphoma (DLBCL). Consensus clustering was performed to molecularly discriminate DLBCL subtypesbased on m(6)A regulators' expression. Using the Cox and Lasso regression algorithm, survival-associated m(6)A regulators were identified, and a m(6)A-based prognostic signature was established. The influence of m(6)A risk on immune cell infiltration, immune checkpoint genes, cancer immunity cycle, and immunotherapeutic response was evaluated. Potential molecular pathways related to m(6)A risk were investigated using gene set enrichment analysis. The m(6)A regulators showed satisfactory performance in distinguishing DLBCL subgroups with distinct clinical traits and outcomes. A six m(6)A regulator-based prognostic signature was established and validated as an independent predictor, which separated patients into low- and high-risk groups. High-risk m(6)A indicated worse survival. The B cells naive, T cells gamma delta, and NK cells resting were the three most affected immune cells by m(6)A risk. Up-regulated (PDCD1 and KIR3DL1) and down-regulated (TIGIT, IDO1, and BTLA) immune checkpoint genes in the high-risk group were identified. The m(6)A risk was found to influence several steps in the cancer immunity cycle. Patients with high-risk m(6)A were more likely to benefit from immunotherapy. Biological function enrichment analysis revealed that high-risk m(6)A to be tended related to malignant tumor characteristics, while low-risk m(6)A showed trend to be related to defensive response processes. Collectively, the m(6)A-based prognostic signature could be a practical prognostic predictor for DLBCL and immune microenvironment characteristics affected by m(6)A may be part of the mechanism.