E3 泛素连接酶相关基因的系统分析确定 UBE2L3 为急性髓系白血病中与耐药相关的预后生物标志物。
Systematic Analysis of E3 Ligase-Related Genes Identified UBE2L3 as a Prognostic Biomarker Associated With Drug Resistance in Acute Myeloid Leukemia.
作者信息
Ling Chun, Cao Nengneng, Wang Huiping, Wan Yang, Liang Xue, Guo Jinjing, Xiao Meng, Zhang Qiguo, Zhai Zhimin
机构信息
Department of Hematology, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230000, People's Republic of China.
Department of Hematology, Affiliated Chuzhou Hospital of Anhui Medical University, First People's Hospital of Chuzhou, Chuzhou, Anhui, 239001, People's Republic of China.
出版信息
Int J Gen Med. 2025 Jan 29;18:459-472. doi: 10.2147/IJGM.S502644. eCollection 2025.
BACKGROUND
Acute Myeloid Leukemia (AML) is a prevalent neoplastic disorder. The roles of E3 ubiquitin ligases and related genes in AML drug resistance and prognosis remain unclear.
METHODS
Genes were identified from GeneCards and UniProt databases, differentially expressed genes were selected based on transcriptional sequencing data from wild-type and Adriamycin-resistant HL60 (HL60/WT & HL60/ADR) cell lines, and the intersection of these three sources was taken. We then constructed a prognostic model comprising five genes (HBP1, RNF130, RMND5B, TRIM32, and UBE2L3) through univariate Cox and LASSO regression analyses in the TCGA cohort and validated it in the BeatAML2.0 cohort. Finally, the expression of UBE2L3 was verified in cell lines and clinical case specimens.
RESULTS
The model accurately predicted AML prognosis and identified the UBE2L3 gene within the model as a high-risk biomarker associated with drug resistance, significantly influencing AML outcomes.
CONCLUSION
The high expression of UBE2L3 is a reliable biomarker for drug resistance and poor prognosis of acute myeloid leukemia.
背景
急性髓系白血病（AML）是一种常见的肿瘤性疾病。E3泛素连接酶及相关基因在AML耐药性和预后中的作用仍不清楚。
方法
从GeneCards和UniProt数据库中鉴定基因，根据野生型和阿霉素耐药HL60（HL60/WT和HL60/ADR）细胞系的转录测序数据选择差异表达基因，并取这三个来源的交集。然后，我们通过单变量Cox和LASSO回归分析在TCGA队列中构建了一个包含五个基因（HBP1、RNF130、RMND5B、TRIM32和UBE2L3）的预后模型，并在BeatAML2.0队列中进行了验证。最后，在细胞系和临床病例标本中验证了UBE2L3的表达。
结果
该模型准确预测了AML的预后，并确定模型中的UBE2L3基因为与耐药性相关的高危生物标志物，显著影响AML的预后。
结论
UBE2L3的高表达是急性髓系白血病耐药和预后不良的可靠生物标志物。
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