Data_Sheet_1_Prediction of prognosis and immunotherapy response of amino acid metabolism genes in acute myeloid leukemia.docx

BackgroundAmino acid (AA) metabolism plays a crucial role in cancer. However, its role in acute myeloid leukemia (AML) is still unavailable. We screened out AA metabolic genes, which related to prognosis, and analyzed their correlation with tumor immune microenvironment in AML.MethodsWe evaluated 472 amino acid metabolism-related genes in 132 AML patients. The predictive risk model was developed according to differentially expressed genes, univariate Cox and LASSO analyses. We validated the risk signature by survival analysis and independence tests. Single-sample gene set enrichment analysis (ssGSEA), tumor immune microenvironment (TME), tumor mutation burden (TMB), functional enrichment, and the IC50 of drugs were assessed to explore the correlations among the risk model, immunity, and drug sensitivity of AML.ResultsSix amino acid metabolism-related genes were confirmed to develop the risk model, including TRH, HNMT, TFEB, SDSL, SLC43A2, and SFXN3. The high-risk subgroup had an immune “hot” phenotype and was related to a poor prognosis. The high-risk group was also associated with more activity of immune cells, such as Tregs, had higher expression of some immune checkpoints, including PD1 and CTLA4, and might be more susceptible to immunotherapy. Xenobiotic metabolism, the reactive oxygen species (ROS) pathway, fatty acid metabolism, JAK/STAT3, and the inflammatory response were active in the high-risk subgroup. Furthermore, the high-risk subgroup was sensitive to sorafenib, selumetinib, and entospletinib. ssGSEA discovered that the processes of glutamine, arginine, tryptophan, cysteine, histidine, L-serine, isoleucine, threonine, tyrosine, and L-phenylalanine metabolism were more active in the high-risk subgroup.ConclusionThis study revealed that AA metabolism-related genes were correlated with the immune microenvironment of AML patients and could predict the prognosis and immunotherapy response of AML patients.

背景：氨基酸（AA）代谢在癌症的发生发展中扮演着至关重要的角色。然而，其在急性髓系白血病（AML）中的作用尚不明确。本研究筛选出与预后相关的氨基酸代谢基因，并分析了其在AML肿瘤免疫微环境中的相关性。方法：我们对132例AML患者的472个氨基酸代谢相关基因进行了评估，根据差异表达基因、单因素Cox和LASSO分析，建立了预测风险模型。通过生存分析和独立性检验验证了风险特征。通过单样本基因集富集分析（ssGSEA）、肿瘤免疫微环境（TME）、肿瘤突变负荷（TMB）、功能富集和药物的IC50值评估，探讨了风险模型、免疫和AML的药物敏感性之间的关系。结果：确认了6个氨基酸代谢相关基因与风险模型相关，包括TRH、HNMT、TFEB、SDSL、SLC43A2和SFXN3。高风险亚组表现出免疫“热”表型，与不良预后相关。高风险组还与免疫细胞，如Tregs的活性增加有关，某些免疫检查点（如PD1和CTLA4）的表达升高，可能对免疫治疗更为敏感。在高风险亚组中，异物代谢、活性氧（ROS）途径、脂肪酸代谢、JAK/STAT3和炎症反应均处于活跃状态。此外，高风险亚组对索拉非尼、塞来昔布和恩托斯普莱汀的敏感性较高。ssGSEA发现，谷氨酰胺、精氨酸、色氨酸、半胱氨酸、组氨酸、L-丝氨酸、异亮氨酸、苏氨酸、酪氨酸和L-苯丙氨酸的代谢过程在高风险亚组中更为活跃。结论：本研究揭示了氨基酸代谢相关基因与AML患者的免疫微环境相关，并能预测AML患者的预后和免疫治疗反应。