Zhanjiang Institute of Clinical Medicine, Central People's Hospital of Zhanjiang, Guangdong Medical University Zhanjiang Central Hospital, Zhanjiang, China.
Department of Laboratory Medicine, Central People's Hospital of Zhanjiang, Guangdong Medical University Zhanjiang Central Hospital, Zhanjiang, China.
J Cell Mol Med. 2024 Aug;28(16):e70017. doi: 10.1111/jcmm.70017.
Acute myeloid leukaemia (AML) is a common and highly aggressive haematological malignancy in adults. Senescence-associated secretory phenotype (SASP) plays important roles in tumorigenesis and progression of tumour. However, the prognostic value of SASP in patients with AML has not been clarified. The present study aims to explore the prognostic value of SASP and develop a prognostic risk signature for AML. The RNA-sequencing data was collected from the TCGA, GTEx and TARGET databases. Subsequently, differentially expressed gene analysis, univariate Cox regression and LASSO regression were applied to identified prognostic SASP-related genes and construct a prognostic risk-scoring model. The risk score of each patient were calculated and patients were divided into high- or low-risk groups by the median risk score. This novel prognostic signature included 11 genes: G6PD, CDK4, RPS6KA1, UBC, H2BC12, KIR2DL4, HSF1, IFIT3, PIM1, RUNX3 and TRIM21. The patients with AML in the high-risk group had shorter OS, demonstrating that the risk score acted as a prognostic predictor, which was validated in the TAGET-AML dataset. Univariate and multivariate analysis revealed the risk score was an independent prognostic factor in patients with AML. Furthermore, the present study revealed that the risk score was associated with immune landscape, immune checkpoint gene expression and chemotherapeutic efficacy. In the present study, we constructed and validated a unique SASP-related prognostic model to assess therapeutic effect and prognosis in patients with AML, which might contribute to understanding the role of SASP in AML and guiding the treatment for AML.
急性髓系白血病（AML）是一种常见且高度侵袭性的成人血液系统恶性肿瘤。衰老相关分泌表型（SASP）在肿瘤的发生和进展中起着重要作用。然而，SASP 在 AML 患者中的预后价值尚未阐明。本研究旨在探讨 SASP 的预后价值，并为 AML 开发一个预后风险特征签名。从 TCGA、GTEx 和 TARGET 数据库中收集了 RNA 测序数据。随后，进行差异表达基因分析、单因素 Cox 回归和 LASSO 回归，以鉴定与 SASP 相关的预后基因，并构建预后风险评分模型。计算每位患者的风险评分，并通过中位数风险评分将患者分为高风险或低风险组。这个新的预后特征签名包括 11 个基因：G6PD、CDK4、RPS6KA1、UBC、H2BC12、KIR2DL4、HSF1、IFIT3、PIM1、RUNX3 和 TRIM21。高风险组的 AML 患者的 OS 更短，表明风险评分可作为预后预测指标，在 TARGET-AML 数据集得到验证。单因素和多因素分析表明，风险评分是 AML 患者的独立预后因素。此外，本研究还揭示了风险评分与免疫景观、免疫检查点基因表达和化疗疗效相关。在本研究中，我们构建并验证了一个独特的 SASP 相关预后模型，以评估 AML 患者的治疗效果和预后，这可能有助于了解 SASP 在 AML 中的作用，并指导 AML 的治疗。
