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急性髓系白血病内质网应激相关预后模型和免疫细胞浸润的生物信息学分析。

Bioinformatics analysis of the endoplasmic reticulum stress-related prognostic model and immune cell infiltration in acute myeloid leukemia.

机构信息

Department of Hematology, The First Affiliated Hospital of Anhui Medical University, Hefei, People's Republic of China.

出版信息

Hematology. 2023 Dec;28(1):2221101. doi: 10.1080/16078454.2023.2221101.

Abstract

BACKGROUND

Acute myeloid leukemia (AML) is the most common malignant hematological disease originating from hematopoietic stem cells. Endoplasmic reticulum stress (ERs) has been reported to be involved in multiple tumor-related biological processes. However, the prognostic role of ERs-related genes in AML has not been fully investigated.

METHODS

The TCGA-LAML RNA-seq dataset was downloaded from the UCSC Xena website as the training cohort. Univariate Cox regression analysis was used to identify 42 ER stress-related genes associated with prognosis. Then, a ERs risk score prognostic model was established through LASSO regression analysis. AML patients were divided into high- and low-risk groups according to the median risk score. The Kaplan-Meier survival curve, time ROC curve analysis and univariate and multivariate independent prognostic analyses were presented for the high- and low-risk groups. Moreover, we verified the ERs risk model in the TARGET-AML and GSE37642 datasets. Next, we performed immune cell infiltration analysis, immune checkpoint gene expression analysis and drug sensitivity analysis.

RESULTS

We found 42 ER stress-related genes with prognostic significance, and a prognostic model consisting of 13 genes was constructed and verified. The survival rate of AML patients in the low-risk group was better than that in the high-risk group. The tumor microenvironment and immune cell infiltration results showed that immune cell infiltration was correlated with the survival status of patients.

CONCLUSION

This research identified a ERs risk model with significant prognostic value. These genes are expected to be potential prognostic biomarkers in AML, providing a new theoretical basis for disease management.

摘要

背景

急性髓系白血病(AML)是最常见的起源于造血干细胞的恶性血液系统疾病。内质网应激(ERs)已被报道参与多种与肿瘤相关的生物学过程。然而,ERs 相关基因在 AML 中的预后作用尚未得到充分研究。

方法

从 UCSC Xena 网站下载 TCGA-LAML RNA-seq 数据集作为训练队列。采用单因素 Cox 回归分析筛选出 42 个与预后相关的 ER 应激相关基因。然后,通过 LASSO 回归分析建立 ERs 风险评分预后模型。根据中位风险评分将 AML 患者分为高低风险组。绘制 Kaplan-Meier 生存曲线、时间 ROC 曲线分析以及单因素和多因素独立预后分析。此外,我们在 TARGET-AML 和 GSE37642 数据集验证了 ERs 风险模型。接下来,我们进行了免疫细胞浸润分析、免疫检查点基因表达分析和药物敏感性分析。

结果

我们发现了 42 个具有预后意义的 ER 应激相关基因,并构建和验证了一个由 13 个基因组成的预后模型。低风险组 AML 患者的生存率优于高风险组。肿瘤微环境和免疫细胞浸润结果表明,免疫细胞浸润与患者的生存状态相关。

结论

本研究确定了一个具有显著预后价值的 ERs 风险模型。这些基因有望成为 AML 潜在的预后生物标志物,为疾病管理提供新的理论依据。

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