Department of Clinical Laboratory, Jiangxi Province Key Laboratory of Laboratory Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
School of Public Health, Nanchang University, Nanchang, Jiangxi, China.
Aging (Albany NY). 2023 Oct 13;15(20):11217-11226. doi: 10.18632/aging.205123.
Cellular senescence is closely related to the occurrence, development, and immune regulation of cancer. However, the predictive value of cellular senescence-related signature in clinical outcome and treatment response in acute myeloid leukemia (AML) remains unexplored. By analyzing the expression profile of cellular senescence-related genes (CSRGs) in AML samples in the TCGA database, we found that cellular senescence is closely related to the prognosis and tumor microenvironment of AML patients, and compared with normal samples, the overall expression level of senescent inducing genes in AML samples was down-regulated, while inhibitory genes were up-regulated. The risk score model further constructed and verified based on CSRGs could be used as an independent prognostic predictor for AML patients, and the overall survival (OS) of high-risk patients was significantly shortened. The area under ROC curve (AUC) values for the prediction of 1-, 3- and 5-year OS were 0.759, 0.749, and 0.806, respectively. In addition, patients with high-risk scores are more sensitive to treatment with cytarabine and may benefit from anti-PD-1 immunotherapy. In conclusion, our results suggest that the cellular senescence-related signature is a strong biomarker of immunotherapy response and prognosis in AML.
细胞衰老与癌症的发生、发展和免疫调节密切相关。然而，细胞衰老相关特征在急性髓系白血病（AML）患者的临床结局和治疗反应中的预测价值仍未得到探索。通过分析 TCGA 数据库中 AML 样本中细胞衰老相关基因（CSRGs）的表达谱，我们发现细胞衰老与 AML 患者的预后和肿瘤微环境密切相关，与正常样本相比，AML 样本中衰老诱导基因的整体表达水平下调，而抑制基因上调。进一步基于 CSRGs 构建和验证的风险评分模型可作为 AML 患者的独立预后预测指标，高风险患者的总生存期（OS）明显缩短。预测 1 年、3 年和 5 年 OS 的 ROC 曲线下面积（AUC）值分别为 0.759、0.749 和 0.806。此外，高风险评分的患者对阿糖胞苷治疗更敏感，可能受益于抗 PD-1 免疫治疗。总之，我们的研究结果表明，细胞衰老相关特征是 AML 免疫治疗反应和预后的强有力生物标志物。
