Objective

Treatment of acute myeloid leukemia (AML) remains a challenge. It is urgent to understand the microenvironment to improve therapy and prognosis.

Methods

Bioinformatics methods were used to analyze transcription expression profile of AML patient samples with complete clinical information from UCSC Xena TCGA-AML datasets and validate with GEO datasets. Western blot, qPCR, RNAi and CCK8 assay were used to assay the effect of GPX1 expression on AML cell viability and the expression of genes of interest.

Results

Our analyses revealed that highly expressed GPX1 in AML patients links to unfavorable prognosis. GPX1 expression was positively associated with not only fraction levels of myeloid-derived suppressor cells (MDSCs), monocytes and T cell exhaustion, the expression levels of MDSC markers, MDSC-promoting CCR2 and immune inhibitory checkpoints (TIM3/Gal-9, SIRPα and VISTA), but also negatively with low fraction levels of CD4+ and CD8+ T cells. Silencing GPX1 expression reduced AML cell viability and CCR2 expression. Moreover, GPX1-targetd kinases were PKC family, SRC family, SYK and PAK1, which promote AML progression and the resistance to therapy. Furthermore, Additionally, GPX1-associated prognostic signature (GPS) is an independent risk factor with high area under curve (AUC) values of receiver operating characteristic (ROC) curves. High risk group based on GPS enriched not only with endocytosis which transfers mitochondria to favor AML cell survival in response to chemotherapy, but also NOTCH, WNT and TLR signaling which promote therapy resistance.

Conclusion

Our results revealed the significant involvement of GPX1 in AML immunosuppression via and provided a prognostic signature for AML patients.

中文翻译：

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GPX1 相关预后特征可预测急性髓系白血病患者的不良生存率并参与免疫抑制

客观的

急性髓性白血病 (AML) 的治疗仍然是一个挑战。迫切需要了解微环境以改善治疗和预后。

方法

使用生物信息学方法分析 AML 患者样本的转录表达谱，并使用来自 UCSC Xena TCGA-AML 数据集的完整临床信息，并使用 GEO 数据集进行验证。使用蛋白质印迹、qPCR、RNAi 和 CCK8 测定来测定 GPX1 表达对 AML 细胞活力和感兴趣基因表达的影响。

结果

我们的分析表明，AML 患者中高表达的 GPX1 与不良预后有关。GPX1 表达不仅与髓源性抑制细胞 (MDSC)、单核细胞和 T 细胞耗竭的分数水平、MDSC 标志物的表达水平、促进 MDSC 的 CCR2 和免疫抑制检查点（TIM3/Gal-9、SIRPα 和VISTA)，但也会对低水平的 CD4+ 和 CD8+ T 细胞产生负面影响。沉默 GPX1 表达会降低 AML 细胞活力和 CCR2 表达。此外，GPX1 靶向激酶是 PKC 家族、SRC 家族、SYK 和 PAK1，它们促进 AML 进展和对治疗的抵抗。此外，此外，GPX1 相关的预后特征 (GPS) 是一个独立的风险因素，具有较高的受试者工作特征 (ROC) 曲线的曲线下面积 (AUC) 值。

结论

我们的结果揭示了 GPX1 在 AML 免疫抑制中的显着参与，并为 AML 患者提供了预后特征。