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KIR2DL 家族可作为急性髓系白血病的预后生物标志物,并与免疫浸润相关。

The KIR2DL family serves as prognostic biomarkers and correlates with immune infiltrates in acute myeloid leukaemia.

机构信息

The First Clinical Medical College of Lanzhou University, Lanzhou, China.

Affiliated Hospital of Qinghai University, Xining, China.

出版信息

J Cell Mol Med. 2024 Apr;28(8):e18256. doi: 10.1111/jcmm.18256.

Abstract

Acute myeloid leukaemia (AML) is a prevalent haematological malignancy in which various immune and stromal cells in the bone marrow microenvironment have instrumental roles and substantially influence its progression. KIR2DL is a member of the immunoglobulin-like receptor family and a natural killer (NK) cell surface-specific receptor. However, its impact on immune infiltration regarding AML has not been addressed. We aimed to explore molecular markers associated with the immune microenvironment and prognosis of AML with a particular focus on KIR2DL family members. Analysis of data from The Cancer Genome Atlas and Genotype-Tissue Expression databases revealed that KIR2DL1, KIR2DL3 and KIR2DL4 expression were significantly upregulated in AML and associated with decreased overall survival (OS). Moreover, univariate Cox analysis implicated KIR2DL genes as independent prognostic markers of OS. Functional enrichment analysis revealed that KIR2DL genes were associated with immune cells, the immune microenvironment and NK cell-mediated cytotoxicity. Additionally, immune infiltration analyses revealed that KIR2DL upregulation was associated with stronger immune infiltration. Finally, we performed drug sensitivity profiling of KIR2DL genes using the Cellminer database. Collectively, our findings suggest that KIR2DL1, KIR2DL3 and KIR2DL4 have critical roles in AML and may represent novel biomarker genes for disease prognosis and immune infiltration.

摘要

急性髓系白血病(AML)是一种常见的血液系统恶性肿瘤,骨髓微环境中的各种免疫细胞和基质细胞在其中发挥重要作用,并对其进展产生重大影响。KIR2DL 是免疫球蛋白样受体家族的成员,也是自然杀伤(NK)细胞表面的特异性受体。然而,其对 AML 免疫浸润的影响尚未得到解决。我们旨在探讨与 AML 免疫微环境和预后相关的分子标志物,特别关注 KIR2DL 家族成员。对癌症基因组图谱和基因型组织表达数据库的数据进行分析后发现,AML 中 KIR2DL1、KIR2DL3 和 KIR2DL4 的表达显著上调,且与总生存期(OS)降低有关。此外,单因素 Cox 分析表明 KIR2DL 基因是 OS 的独立预后标志物。功能富集分析表明,KIR2DL 基因与免疫细胞、免疫微环境和 NK 细胞介导的细胞毒性有关。此外,免疫浸润分析显示,KIR2DL 上调与更强的免疫浸润有关。最后,我们使用 Cellminer 数据库对 KIR2DL 基因进行了药物敏感性分析。综上所述,我们的研究结果表明,KIR2DL1、KIR2DL3 和 KIR2DL4 在 AML 中具有关键作用,可能成为疾病预后和免疫浸润的新型生物标志物基因。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/195f/10963068/8da25437cfec/JCMM-28-e18256-g001.jpg

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