Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, No.79 Qingchun Rd, Hangzhou, 310006, Zhejiang, China.
Institute of Hematology, Zhejiang University, Hangzhou, Zhejiang, China.
Cancer Immunol Immunother. 2019 Dec;68(12):1971-1978. doi: 10.1007/s00262-019-02408-7. Epub 2019 Oct 24.
Acute myeloid leukemia (AML) is a common and lethal hematopoietic malignancy that is highly dependent on the bone marrow (BM) microenvironment. Infiltrating immune and stromal cells are important components of the BM microenvironment and significantly influence the progression of AML. This study aimed to elucidate the value of immune/stromal cell-associated genes for AML prognosis by integrated bioinformatics analysis. We obtained expression profiles from The Cancer Genome Atlas (TCGA) database and used the ESTIMATE algorithm to calculate immune scores and stromal scores; we then identified differentially expressed genes (DEGs) based on these scores. Overall survival analysis was applied to reveal common DEGs of prognostic value. Subsequently, we conducted a functional enrichment analysis, generated a protein-protein interaction (PPI) network and performed an interrelation analysis of immune system processes, showing that these genes are mainly associated with the immune/inflammatory response. Finally, eight genes (CD163, CYP27A1, KCNA5, PPM1J, FOLR1, IL1R2, MYOF, VSIG2) were verified to be significantly associated with AML prognosis in the Gene Expression Omnibus (GEO) database. In summary, we identified key microenvironment-related genes that affect the outcomes of AML patients and might serve as therapeutic targets.
急性髓系白血病（AML）是一种常见且致命的造血恶性肿瘤，高度依赖骨髓（BM）微环境。浸润的免疫细胞和基质细胞是 BM 微环境的重要组成部分，显著影响 AML 的进展。本研究旨在通过综合生物信息学分析阐明免疫/基质细胞相关基因对 AML 预后的价值。我们从癌症基因组图谱（TCGA）数据库中获取了表达谱，并使用 ESTIMATE 算法计算了免疫评分和基质评分；然后根据这些评分确定差异表达基因（DEGs）。进行总体生存分析以揭示具有预后价值的常见 DEGs。随后，我们进行了功能富集分析，生成了蛋白质-蛋白质相互作用（PPI）网络，并对免疫系统过程的相互关系进行了分析，结果表明这些基因主要与免疫/炎症反应有关。最后，在基因表达综合数据库（GEO）中验证了 8 个基因（CD163、CYP27A1、KCNA5、PPM1J、FOLR1、IL1R2、MYOF、VSIG2）与 AML 预后显著相关。总之，我们确定了关键的与微环境相关的基因，这些基因影响 AML 患者的结局，可能成为治疗靶点。
