National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China.
Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China.
Aging (Albany NY). 2023 Jun 26;15(12):5826-5853. doi: 10.18632/aging.204843.
To explore effects of aging-related genes (ARGs) on the prognosis of Acute Myeloid Leukemia (AML), a seven-ARGs signature was developed and validated in AML patients. The numbers of seven-ARG sequences were selected to construct the survival prognostic signature in TCGA-LAML cohort, and two GEO datasets were used independently to verify the prognostic values of signature. According to seven-ARGs signature, patients were categorized into two subgroups. Patients with high-risk prognostic score were defined as HRPS-group/high-risk group, while others were set as LRPS-group/low-risk group. HRPS-group presented adverse overall survival (OS) than LRPS-group in TCGA-AML cohort (HR=3.39, <0.001). In validation, the results emphasized a satisfactory discrimination in different time points, and confirmed the poor OS of HRPS-group both in GSE37642 (HR=1.96, =0.001) and GSE106291 (HR=1.88, <0.001). Many signal pathways, including immune- and tumor-related processes, especially signaling, were highly enriched in HRPS-group. Coupled with high immune-inflamed infiltration, the HRPS-group was highly associated with the driver gene and oncogenic signaling pathway of . Prediction of blockade therapy targeting immune checkpoint indicated varied benefits base on the different ARGs signature score, and the results of predicted drug response suggested that Pevonedistat, an inhibitor of -activating enzyme, targeting signaling, may have potential therapeutic value for HRPS-group. Compared with clinical factors alone, the signature had an independent value and more predictive power of AML prognosis. The 7-ARGs signature may help to guide clinical-decision making to predict drug response, and survival in AML patients.
为了探究与衰老相关基因（ARGs）对急性髓系白血病（AML）预后的影响，本研究构建了一个包含七个 ARGs 的签名，并在 AML 患者中进行了验证。在 TCGA-LAML 队列中，通过选择七个 ARG 序列的数量来构建生存预后签名，并使用两个 GEO 数据集独立验证了该签名的预后价值。根据七个 ARGs 签名，患者被分为两个亚组。高风险预后评分组（HRPS-group/高风险组）定义为具有高风险预后评分的患者，而低风险预后评分组（LRPS-group/低风险组）定义为其他患者。在 TCGA-AML 队列中，HRPS-group 的总生存（OS）明显差于 LRPS-group（HR=3.39，<0.001）。在验证中，该结果在不同时间点均表现出良好的区分能力，并证实了 HRPS-group 在 GSE37642（HR=1.96，=0.001）和 GSE106291（HR=1.88，<0.001）中 OS 较差。许多信号通路，包括免疫和肿瘤相关过程，特别是 信号通路，在 HRPS-group 中高度富集。与高免疫浸润相关，HRPS-group 与 AML 的驱动基因和致癌信号通路密切相关。针对免疫检查点阻断治疗的预测表明，基于不同的 ARGs 签名评分，获益情况各不相同，预测药物反应的结果表明，针对 信号通路的 -激活酶抑制剂 Pevonedistat 可能对 HRPS-group 具有潜在的治疗价值。与临床因素单独相比，该签名对 AML 预后具有独立的价值和更高的预测能力。该 7-ARGs 签名可能有助于指导临床决策，预测 AML 患者的药物反应和生存情况。
