Zhu Kai, Lang Zhichao, Zhan Yating, Tao Qiqi, Yu Zhijie, Chen Lili, Fan Congcong, Jin Yan, Yu Kang, Zhu Bihan, Gao Yuxiang, Wang Chengchi, Jiang Songfu, Shi Yifen
Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Department of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Front Oncol. 2022 Oct 20;12:1023040. doi: 10.3389/fonc.2022.1023040. eCollection 2022.
Acute myeloid leukemia (AML) is one of the most common hematopoietic malignancies and exhibits a high rate of relapse and unfavorable outcomes. Ferroptosis, a relatively recently described type of cell death, has been reported to be involved in cancer development. However, the prognostic value of ferroptosis-related genes (FRGs) in AML remains unclear. In this study, we found 54 differentially expressed ferroptosis-related genes (DEFRGs) between AML and normal marrow tissues. 18 of 54 DEFRGs were correlated with overall survival (OS) (P<0.05). Using the least absolute shrinkage and selection operator (LASSO) Cox regression analysis, we selected 10 DEFRGs that were associated with OS to build a prognostic signature. Data from AML patients from the International Cancer Genome Consortium (ICGC) cohort as well as the First Affiliated Hospital of Wenzhou Medical University (FAHWMU) cohort were used for validation. Notably, the prognostic survival analyses of this signature passed with a significant margin, and the riskscore was identified as an independent prognostic marker using Cox regression analyses. Then we used a machine learning method (SHAP) to judge the importance of each feature in this 10-gene signature. Riskscore was shown to have the highest correlation with this 10-gene signature compared with each gene in this signature. Further studies showed that AML was significantly associated with immune cell infiltration. In addition, drug-sensitive analysis showed that 8 drugs may be beneficial for treatment of AML. Finally, the expressions of 10 genes in this signature were verified by real-time quantitative polymerase chain reaction. In conclusion, our study establishes a novel 10-gene prognostic risk signature based on ferroptosis-related genes for AML patients and FRGs may be novel therapeutic targets for AML.
急性髓系白血病（AML）是最常见的造血系统恶性肿瘤之一，具有高复发率和不良预后。铁死亡是一种相对较新描述的细胞死亡类型，据报道其与癌症发展有关。然而，铁死亡相关基因（FRGs）在AML中的预后价值仍不清楚。在本研究中，我们发现AML与正常骨髓组织之间有54个差异表达的铁死亡相关基因（DEFRGs）。54个DEFRGs中的18个与总生存期（OS）相关（P<0.05）。使用最小绝对收缩和选择算子（LASSO）Cox回归分析，我们选择了10个与OS相关的DEFRGs来构建一个预后特征。来自国际癌症基因组联盟（ICGC）队列以及温州医科大学附属第一医院（FAHWMU）队列的AML患者数据用于验证。值得注意的是，该特征的预后生存分析结果差异显著，并且使用Cox回归分析将风险评分确定为独立的预后标志物。然后我们使用机器学习方法（SHAP）来判断这10基因特征中每个特征的重要性。与该特征中的每个基因相比，风险评分与这个10基因特征的相关性最高。进一步研究表明，AML与免疫细胞浸润显著相关。此外，药物敏感性分析表明8种药物可能对AML治疗有益。最后，通过实时定量聚合酶链反应验证了该特征中10个基因的表达。总之，我们的研究基于铁死亡相关基因为AML患者建立了一种新的10基因预后风险特征，并且FRGs可能是AML的新治疗靶点。
