急性髓系白血病患者 SASP 相关预后特征的构建和验证。
Construction and validation of a SASP-related prognostic signature in patients with acute myeloid leukaemia.
发表日期:2024 Aug
作者:
Ming-Feng Li, Dong-Hui Zhang, Li-Si Wang, Cai-Feng Yue, Li-Juan Pang, Yun-Miao Guo, Zhi-Gang Yang
来源:
GENES & DEVELOPMENT
摘要:
急性髓系白血病(AML)是成人中一种常见且高度侵袭性的血液恶性肿瘤。衰老相关分泌表型(SASP)在肿瘤发生和进展中发挥重要作用。然而,SASP 对 AML 患者的预后价值尚未明确。本研究旨在探讨 SASP 的预后价值并开发 AML 的预后风险特征。 RNA 测序数据是从 TCGA、GTEx 和 TARGET 数据库收集的。随后,应用差异表达基因分析、单变量Cox回归和LASSO回归来鉴定预后SASP相关基因并构建预后风险评分模型。计算每位患者的风险评分,并根据中位风险评分将患者分为高风险组或低风险组。这种新的预后特征包括 11 个基因:G6PD、CDK4、RPS6KA1、UBC、H2BC12、KIR2DL4、HSF1、IFIT3、PIM1、RUNX3 和 TRIM21。高风险组中的 AML 患者的 OS 较短,这表明风险评分可以作为预后预测因子,这一点在 TAGET-AML 数据集中得到了验证。单变量和多变量分析显示风险评分是 AML 患者的独立预后因素。此外,本研究表明,风险评分与免疫状况、免疫检查点基因表达和化疗效果相关。在本研究中,我们构建并验证了一个独特的 SASP 相关预后模型来评估 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。© 2024 作者( s)。细胞与分子医学基金会和约翰·威利出版的《细胞与分子医学杂志》
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.© 2024 The Author(s). Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.