阐明TP53基因突变的急性髓性白血病的免疫格局和潜在预后模型

IF 2 4区 医学 Q3 HEMATOLOGY Hematology Pub Date : 2024-12-01 Epub Date: 2024-09-27 DOI:10.1080/16078454.2024.2400620
Gelan Zhu, Jiayi Cai, Wanbin Fu, Yue Sun, Ting Wang, Hua Zhong
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引用次数: 0

摘要

研究目的TP53突变是一种常见的肿瘤抑制基因改变,与急性髓性白血病(AML)患者的化疗耐药、复发率增加和总生存期(OS)缩短有关:在这项研究中,我们利用《癌症基因组图谱》(The Cancer Genome Atlas,TCGA)数据描述了不同AML队列中TP53突变表型的特征。我们从突变型和野生型TP53急性髓细胞白血病标本的差异表达基因中设计出了TP53相关预后特征。我们对基因变异、免疫细胞浸润和预后分层进行了深入分析:结果:利用最小绝对收缩和选择算子(LASSO)-Cox 回归法建立了六基因 TP53 相关特征,显示出强大的预后预测能力。该特征在 OHSU 验证队列、独立的基因表达总库(GEO)验证队列(GSE71014)中都表现出很强的性能,体内实验结果也证明了这一点。最后,我们利用单细胞数据库(GSE198681)观察了这六个基因的特征:讨论:我们的研究可能有助于开发有效的治疗方法,并为未来的研究提供了新的思路。结论TP53相关特征和模式具有完善预后分层和强调新兴靶向疗法的潜力。
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Elucidating the immune landscape and potential prognostic model in acute myeloid leukemia with TP53 mutation.

Objectives: The TP53 mutation, a prevalent tumor suppressor gene alteration, is linked to chemotherapy resistance, increased relapse rates and diminished overall survival (OS) in acute myeloid leukemia (AML) patients.

Methods: In this study, we characterize the TP53 mutation phenotypes across various AML cohorts utilizing The Cancer Genome Atlas (TCGA) data. We devised a TP53-related prognostic signature derived from differentially expressed genes between mutated and wild-type TP53 AML specimens. In-depth analyses were conducted, encompassing genetic variation, immune cell infiltration and prognostic stratification.

Results: A six-gene TP53-related signature was established using least absolute shrinkage and selection operator (LASSO)-Cox regression, demonstrating robust prognostic predictability. This signature exhibited strong performance in both the OHSU validation cohorts, an independent Gene Expression Omnibus (GEO) validation cohort (GSE71014) and proved by results of the in vivo experiment. Finally, we used single cell database (GSE198681) to observe the characteristics of these six genes.

Discussion: Our study may facilitate the development of efficacious therapeutic approaches and provide a novel idea for future research. Conclusion: The TP53-related signature and pattern hold the potential to refine prognostic stratification and underscore emerging targeted therapies.

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来源期刊
Hematology
Hematology 医学-血液学
CiteScore
2.60
自引率
5.30%
发文量
140
审稿时长
3 months
期刊介绍: Hematology is an international journal publishing original and review articles in the field of general hematology, including oncology, pathology, biology, clinical research and epidemiology. Of the fixed sections, annotations are accepted on any general or scientific field: technical annotations covering current laboratory practice in general hematology, blood transfusion and clinical trials, and current clinical practice reviews the consensus driven areas of care and management.
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