Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, Finland.
Peking University Health Science Center, Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing, China.
Leukemia. 2022 Oct;36(10):2384-2395. doi: 10.1038/s41375-022-01662-6. Epub 2022 Aug 9.
Treatment responses of patients with acute myeloid leukemia (AML) are known to be heterogeneous, posing challenges for risk scoring and treatment stratification. In this retrospective multi-cohort study, we investigated whether combining pyroptosis- and immune-related genes improves prognostic classification of AML patients. Using a robust gene pairing approach, which effectively eliminates batch effects across heterogeneous patient cohorts and transcriptomic data, we developed an immunity and pyroptosis-related prognostic (IPRP) signature that consists of 15 genes. Using 5 AML cohorts (n = 1327 patients total), we demonstrate that the IPRP score leads to more consistent and accurate survival prediction performance, compared with 10 existing signatures, and that IPRP scoring is widely applicable to various patient cohorts, treatment procedures and transcriptomic technologies. Compared to current standards for AML patient stratification, such as age or ELN2017 risk classification, we demonstrate an added prognostic value of the IPRP risk score for providing improved prediction of AML patients. Our web-tool implementation of the IPRP score and a simple 4-factor nomogram enables practical and robust risk scoring for AML patients. Even though developed for AML patients, our pan-cancer analyses demonstrate a wider application of the IPRP signature for prognostic prediction and analysis of tumor-immune interplay also in multiple solid tumors.
治疗反应的急性髓系白血病（AML）患者已知的是异构的，为风险评分和治疗分层带来挑战。在这项回顾性多队列研究中，我们研究了是否结合细胞焦亡和免疫相关基因可以改善 AML 患者的预后分类。使用稳健的基因配对方法，该方法可以有效地消除不同患者队列和转录组数据之间的批次效应，我们开发了一个由 15 个基因组成的免疫和细胞焦亡相关预后（IPRP）特征。使用 5 个 AML 队列（n=1327 例患者），我们证明与 10 个现有特征相比，IPRP 评分可实现更一致和准确的生存预测性能，并且 IPRP 评分广泛适用于各种患者队列、治疗程序和转录组技术。与 AML 患者分层的当前标准（如年龄或 ELN2017 风险分类）相比，我们证明了 IPRP 风险评分的预后价值增加，可改善 AML 患者的预测。我们的 IPRP 评分的网络工具实现和简单的 4 因素列线图为 AML 患者提供了实用且稳健的风险评分。尽管是为 AML 患者开发的，但我们的泛癌分析表明，IPRP 特征在多个实体瘤中也可更广泛地用于预后预测和肿瘤免疫相互作用分析。
