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基于铜死亡相关基因探索急性髓系白血病患者的预后标志物

Exploring prognostic markers for patients with acute myeloid leukemia based on cuproptosis related genes.

作者信息

Li Xinyue, Xu Lianrong

机构信息

Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan, China.

Department of Hematology, 2nd Hospital of Shanxi Medical University, Taiyuan, China.

出版信息

Transl Cancer Res. 2023 Aug 31;12(8):2008-2022. doi: 10.21037/tcr-23-85. Epub 2023 Aug 28.

Abstract

BACKGROUND

Acute myeloid leukemia (AML), a common form of acute leukemia, is due to tumor changes and clonal proliferation caused by genetic variants. Cuproptosis is a novel form of regulated cell death. This study aimed to explore the role of cuproptosis-related genes (CRGs) in AML.

METHODS

Initially, differentially expressed genes (DEGs) between AML samples and normal samples were obtained by differential analysis, which were further intersected with the cuproptosis score-related genes (CSRGs) acquired by weighted gene co-expression network analysis (WGCNA) to obtain cuproptosis score-related differentially expressed genes (CS-DEGs). Then, a risk model was constructed by Cox analysis and least absolute shrinkage and selection operator (LASSO) analysis. Finally, immune infiltration analysis was performed and the functions and pathways of model genes were explored by single sample gene set enrichment analysis (ssGSEA).

RESULTS

Thirty-two CS-DEGs were obtained by overlapping 11,160 DEGs and 132 CSRGs. These 32 CS-DEGs were mainly enriched to cytoplasmic microtubule organization, RNA methylation, mTOR signaling pathway, and notch signaling pathway. Two model genes, and , were finally screened for the construction of the risk model. In addition, and were significantly positively correlated with activated B cells, CD56dim natural killer (NK) cells, and negatively correlated with effector memory CD4 T cells and activated CD4 T cells. gene was significantly enriched to inositol phosphate metabolism, histone modification, etc. was mainly enriched to ncRNA metabolic process, 2-oxocarboxylic acid metabolism, and other pathways.

CONCLUSIONS

A cuproptosis-related risk model consisting of and was built, which provided a new direction for the diagnosis and treatment of AML.

摘要

背景

急性髓系白血病(AML)是急性白血病的常见形式,由基因变异导致的肿瘤变化和克隆增殖引起。铜死亡是一种新型的程序性细胞死亡形式。本研究旨在探讨铜死亡相关基因(CRGs)在AML中的作用。

方法

首先,通过差异分析获得AML样本与正常样本之间的差异表达基因(DEGs),并将其与通过加权基因共表达网络分析(WGCNA)获得的铜死亡评分相关基因(CSRGs)进一步交叉,以获得铜死亡评分相关差异表达基因(CS-DEGs)。然后,通过Cox分析和最小绝对收缩和选择算子(LASSO)分析构建风险模型。最后,进行免疫浸润分析,并通过单样本基因集富集分析(ssGSEA)探索模型基因的功能和通路。

结果

通过重叠11,160个DEGs和132个CSRGs获得了32个CS-DEGs。这32个CS-DEGs主要富集于细胞质微管组织、RNA甲基化、mTOR信号通路和Notch信号通路。最终筛选出两个模型基因用于构建风险模型。此外,[具体基因1]和[具体基因2]与活化B细胞、CD56dim自然杀伤(NK)细胞显著正相关,与效应记忆CD4 T细胞和活化CD4 T细胞显著负相关。[具体基因1]基因显著富集于肌醇磷酸代谢、组蛋白修饰等。[具体基因2]主要富集于非编码RNA代谢过程、2-氧代羧酸代谢等通路。

结论

构建了一个由[具体基因1]和[具体基因2]组成的铜死亡相关风险模型,为AML的诊断和治疗提供了新方向。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80ea/10493802/c5323194b936/tcr-12-08-2008-f1.jpg

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