Identification and validation of a 7-genes prognostic signature for adult acute myeloid leukemia based on aging-related genes.
Identification and validation of a 7-genes prognostic signature for adult acute myeloid leukemia based on aging-related genes.
复制标题
基于衰老相关基因的成人急性髓系白血病的 7 个基因预后特征的鉴定和验证。
DOI：
10.18632/aging.204843
复制
发表时间：
2023-06-26
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
--
作者：
为了探讨衰老相关基因（ARGs）对急性髓性白血病（AML）预后的影响，研究人员在AML患者中开发并验证了7个ARGs特征。选择7个arg序列的数量构建TCGA-LAML队列的生存预后特征，并独立使用两个GEO数据集验证特征的预后价值。根据7个args特征，将患者分为两个亚组。高危预后评分患者定义为hrps组/高危组，其余患者定义为lrpps组/低危组。在TCGA-AML队列中，hrps组总生存期（OS）低于lps组（HR=3.39， P<0.001）。在验证中，结果强调了不同时间点的良好区分，并证实了hrps组在GSE37642 （HR=1.96， P=0.001）和GSE106291 （HR=1.88， P<0.001）均存在较差的OS。许多信号通路，包括免疫和肿瘤相关的过程，特别是NF-κ b信号，在hrps组中高度富集。hrps组伴高免疫炎症浸润，与TP53驱动基因及致癌信号通路高度相关。针对免疫检查点的阻断治疗预测，根据ARGs特征评分的不同，获益不同，预测药物反应的结果提示Pevonedistat，一种针对NF-κB信号通路的nedd8活化酶抑制剂，可能对hrps组有潜在的治疗价值。与单独的临床因素相比，该特征对AML预后具有独立的预测价值和更强的预测能力。7-ARGs特征可能有助于指导临床决策，以预测AML患者的药物反应和生存。
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, P<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, P=0.001) and GSE106291 (HR=1.88, P<0.001). Many signal pathways, including immune- and tumor-related processes, especially NF-κB 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 TP53. 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 NEDD8-activating enzyme, targeting NF-κB 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.
登录
查看更多内容
影响因子：
20.3
作者：
Guzman, ML;Neering, SJ;Jordan, CT
通讯作者：
Jordan, CT
影响因子：
6.2
作者：
Alibhai, Shabbir M. H.;Leach, Marc;Brandwein, Joseph
通讯作者：
Brandwein, Joseph
影响因子：
5.2
作者：
Huang, Shaoxin;Zhang, Biyu;Fu, Denggang
通讯作者：
Fu, Denggang
影响因子：
20.3
作者：
Frelin, C;Imbert, V;Peyron, JF
通讯作者：
Peyron, JF
影响因子：
0.8
作者：
Ishwaran H;Kogalur UB
通讯作者：
Kogalur UB