Xie Jin-Ye, Wang Wei-Jia, Wang Nan, Dong Qian, Han Hui, Feng Yan-Pin, Yuan Yong, Feng Juan, Chen Kang
Department of Laboratory Medicine, Zhongshan City People's Hospital Zhongshan 528403, Guangdong, China.
Department of Medical Research, Zhongshan City People's Hospital Zhongshan 528403, Guangdong, China.
Am J Transl Res. 2023 Jun 15;15(6):4332-4344. eCollection 2023.
To identify and validate the immune-related gene signature in patients with acute myeloid leukemia (AML).
Differentially expressed genes (DEGs) profiles and survival data were obtained from The Cancer Genome Atlas (TCGA), following screened immune-associated genes from the InnateDB database. Subsequently, the weighted gene co-expression network analysis (WGCNA) was used to detect functional modules, and survival analysis was performed. The least absolute shrinkage and selection operator (LASSO) regression model combined with a partial likelihood-based Cox proportional hazard regression model was applied to select prognostic genes, and the ESTIMATE algorithm was used to construct an immune score-based risk assessment model. Finally, two independent datasets from the Gene Expression Omnibus (GEO) and our clinical data were used for external validation. Moreover, a subpopulation of the immune microenvironment cells was analyzed by the CIBERSORT algorithm, and its related serum indicator was identified by the enzyme-linked immunosorbent assay (ELISA) in clinical samples.
Finally, and were identified as the immune-related gene signature, and the risk stratification model was validated in both the GSE12417 database and our clinical cohort. Furthermore, the fraction of activated mast cells was identified. CIBERSORT algorithm showed that these cells have a positive association with prognosis. In addition, mast cell stimulator IL-33 was markedly decreased in AML patients with poor prognoses.
A novel immune-related gene signature () and its associated plasma indicator (mast cells activator, IL-33) were found to have prognostic value in AML patients.
识别并验证急性髓系白血病(AML)患者的免疫相关基因特征。
从癌症基因组图谱(TCGA)获取差异表达基因(DEG)谱和生存数据,随后从InnateDB数据库中筛选免疫相关基因。接着,使用加权基因共表达网络分析(WGCNA)检测功能模块,并进行生存分析。应用最小绝对收缩和选择算子(LASSO)回归模型结合基于偏似然的Cox比例风险回归模型来选择预后基因,并使用ESTIMATE算法构建基于免疫评分的风险评估模型。最后,使用来自基因表达综合数据库(GEO)的两个独立数据集和我们的临床数据进行外部验证。此外,通过CIBERSORT算法分析免疫微环境细胞亚群,并通过酶联免疫吸附测定(ELISA)在临床样本中鉴定其相关血清指标。
最终,[具体基因名称1]和[具体基因名称2]被确定为免疫相关基因特征,并且风险分层模型在GSE12417数据库和我们的临床队列中均得到验证。此外,还鉴定出活化肥大细胞的比例。CIBERSORT算法显示这些细胞与预后呈正相关。此外,预后不良的AML患者中肥大细胞刺激因子IL-33明显降低。
发现一种新的免疫相关基因特征([具体基因名称1]和[具体基因名称2])及其相关血浆指标(肥大细胞激活剂IL-33)在AML患者中具有预后价值。