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GPR183高表达预示细胞遗传学正常的急性髓系白血病患者预后不良。

High Expression of GPR183 Predicts Poor Survival in Cytogenetically Normal Acute Myeloid Leukemia.

作者信息

Zhuang Haihui, Li Fenglin, Pei Renzhi, Jiang Xia, Chen Dong, Li Shuangyue, Ye Peipei, Yuan Jiaojiao, Lian Jiangyin, Jin Jie, Lu Ying

机构信息

Department of Hematology, The Affiliated People's Hospital of Ningbo University, Ningbo, China.

Institute of Hematology, Ningbo University, Ningbo, China.

出版信息

Biochem Genet. 2025 Jan 16. doi: 10.1007/s10528-025-11026-1.

Abstract

Acute myeloid leukemia (AML) with a normal karyotype (CN-AML) constitutes approximately 50% of all AML cases, presenting significant prognostic variability, and highlighting the urgent need for the identification of novel molecular biomarkers. In this study, we systematically assessed GPR183 expression levels using qRT-PCR in our clinical follow-up study which included 283 CN-AML patients. Using Kaplan-Meier analysis, we found that patients with high GPR183 expression levels exhibited significantly worse overall survival (OS) (P = 0.046) and event-free survival (EFS) (P = 0.030) compared to those with low GPR183 expression. Comprehensive univariate and multivariate Cox regression analyses confirmed that GPR183 expression is a prognostic factor for OS and EFS (P < 0.05). To further validate these findings, we analyzed an independent cohort of 104 CN-AML patients from the GSE71014 dataset, corroborating our primary results, and indicating that high GPR183 expression is associated with poorer survival outcomes. Additionally, RNA-seq data from the GSE71014 dataset were analyzed by Gene Set Enrichment Analysis (GSEA). The results suggested that GPR183 may influence disease progression through the activation of the "TNFa Signaling Via NF-κB" pathway. Collectively, these findings suggested that GPR183 could serve as a valuable prognostic biomarker in CN-AML, offering insights into the underlying mechanisms of disease progression.

摘要

核型正常的急性髓系白血病(CN-AML)约占所有AML病例的50%,其预后存在显著差异,凸显了识别新型分子生物标志物的迫切需求。在本研究中,我们在一项纳入283例CN-AML患者的临床随访研究中,使用qRT-PCR系统评估了GPR183的表达水平。通过Kaplan-Meier分析,我们发现GPR183表达水平高的患者与GPR183表达水平低的患者相比,总生存期(OS)显著更差(P = 0.046),无事件生存期(EFS)也显著更差(P = 0.030)。全面的单因素和多因素Cox回归分析证实,GPR183表达是OS和EFS的预后因素(P < 0.05)。为了进一步验证这些发现,我们分析了来自GSE71014数据集的104例CN-AML患者的独立队列,证实了我们的主要结果,并表明GPR183高表达与较差的生存结果相关。此外,通过基因集富集分析(GSEA)对来自GSE71014数据集的RNA-seq数据进行了分析。结果表明,GPR183可能通过激活“TNFα信号通过NF-κB”途径影响疾病进展。总体而言,这些发现表明GPR183可作为CN-AML中有价值的预后生物标志物,为疾病进展的潜在机制提供了见解。

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