Expression of N6-methyladenosine (m6A) regulators correlates with immune microenvironment characteristics and predicts prognosis in diffuse large cell lymphoma (DLBCL). Issue 1 (1st January 2021) - Xie, Zucheng
ABSTRACT: 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 naïve, 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.