Ren Na, Wang Jianan, Li Ruibing, Yin Chengliang, Li Mianyang, Wang Chengbin
Medical School of Chinese PLA, Beijing, China.
Department of Laboratory Medicine, The First Medical Center of Chinese PLA General Hospital, Beijing, China.
Front Genet. 2024 Oct 3;15:1424365. doi: 10.3389/fgene.2024.1424365. eCollection 2024.
Acute myeloid leukemia(AML) is a diverse malignancy with a prognosis that varies, being especially unfavorable in older patients and those with high-risk characteristics. Metabolic reprogramming has become a significant factor in AML development , presenting new opportunities for prognostic assessment and therapeutic intervention.
Metabolism-related differentially expressed genes (mDEGs) were identified by integrating KEGG metabolic gene lists with AML gene expression data from GSE63270. Using TCGA data, we performed consensus clustering and survival analysis to investigate the prognostic significance of mDEGs. A metabolic risk model was constructed using LASSO Cox reg ression and enhanced by a nomogram incorporated clinical characteristics. The model was validated through receiver operating characteristic (ROC) curves and survival statistics. Gene network analysis was conducted to identify critical prognostic factors. The tumor immune microenvironment was evaluated using CIBERSORT and ESTIMATE algorithms, followed by correlation analysis between immune checkpoint gene expression and risk scores. Drug sensitivity predictions and assays were performed to explore the effects of mDEGs on cell proliferation and chemoresistance.
An 11-gene metabolic prognostic model was established and validated. High-risk patients had worse overall survival in both training and validation cohorts ( < 0.05). The risk score was an independent prognostic factor. High-risk patients showed increased immune cell infiltration and potential response to checkpoint inhibitors but decreased drug sensitivity. The model correlated with sensitivity to drugs such as venetoclax. Carbonic anhydrase 13 (CA13) was identified as a key gene related to prognosis and doxorubicin resistance. Knocking down CA13 reduced proliferation and increased cell death with doxorubicin treatment.
A novel metabolic gene signature was developed to stratify risk and predict prognosis in AML, serving as an independent prognostic factor. CA13 was identified as a potential therapeutic target. This study provides new insights into the prognostic and therapeutic implications of metabolic genes in AML.
急性髓系白血病（AML）是一种异质性恶性肿瘤，其预后各不相同，在老年患者和具有高危特征的患者中尤其不佳。代谢重编程已成为AML发展的一个重要因素，为预后评估和治疗干预带来了新的机遇。
通过将KEGG代谢基因列表与来自GSE63270的AML基因表达数据相结合，鉴定出与代谢相关的差异表达基因（mDEGs）。利用TCGA数据，我们进行了一致性聚类和生存分析，以研究mDEGs的预后意义。使用LASSO Cox回归构建代谢风险模型，并通过纳入临床特征的列线图进行强化。该模型通过受试者工作特征（ROC）曲线和生存统计进行验证。进行基因网络分析以识别关键的预后因素。使用CIBERSORT和ESTIMATE算法评估肿瘤免疫微环境，随后进行免疫检查点基因表达与风险评分之间的相关性分析。进行药物敏感性预测和检测，以探索mDEGs对细胞增殖和化疗耐药性的影响。
建立并验证了一个由11个基因组成的代谢预后模型。高危患者在训练队列和验证队列中的总生存期均较差（<0.05）。风险评分是一个独立的预后因素。高危患者显示免疫细胞浸润增加，对检查点抑制剂有潜在反应，但药物敏感性降低。该模型与对维奈克拉等药物的敏感性相关。碳酸酐酶13（CA13）被鉴定为与预后和阿霉素耐药性相关的关键基因。敲低CA13可减少增殖，并在阿霉素治疗时增加细胞死亡。
开发了一种新的代谢基因特征，用于对AML进行风险分层和预后预测，作为一个独立的预后因素。CA13被鉴定为一个潜在的治疗靶点。本研究为AML中代谢基因的预后和治疗意义提供了新的见解。
