期刊
CANCERS
卷 15, 期 21, 页码 -出版社
MDPI
DOI: 10.3390/cancers15215289
关键词
complex karyotype; AML; MDS; gene expression; SOD1
类别
Complex karyotype (CK) is associated with poor prognosis in AML and MDS-EB, and dysregulated gene expression may be involved. We identified a 10-gene signature (CKS) that accurately predicts CK and is associated with shorter overall survival.
Simple Summary Complex karyotype (CK), defined as >= 3 unrelated chromosomal abnormalities, is associated with a poor prognosis in both acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Despite their high genetic complexity, complex chromosomal abnormalities in AML and MDS may share dysregulated gene expression signatures, leading to poorer outcomes compared to those of standard chemotherapy. We aimed to investigate a subset of genes and their signatures to predict CK in AML and MDS with excess blast (MDS-EB) using gene expression data. The CK signature (CKS) was established and validated, and its prognostic impact on overall survival (OS) was evaluated in comparison with previously reported risk stratification models using gene expression. A 10-gene CKS demonstrated high predictive accuracy for CK and was associated with shorter OS with comparable performance to previously established risk stratification models.Abstract Complex karyotype (CK) is associated with a poor prognosis in both acute myeloid leukemia (AML) and myelodysplastic syndrome with excess blasts (MDS-EB). Transcriptomic analyses have improved our understanding of the disease and risk stratification of myeloid neoplasms; however, CK-specific gene expression signatures have been rarely investigated. In this study, we developed and validated a CK-specific gene expression signature. Differential gene expression analysis between the CK and non-CK groups using data from 348 patients with AML and MDS-EB from four cohorts revealed enrichment of the downregulated genes localized on chromosome 5q or 7q, suggesting that haploinsufficiency due to the deletion of these chromosomes possibly underlies CK pathogenesis. We built a robust transcriptional model for CK prediction using LASSO regression for gene subset selection and validated it using the leave-one-out cross-validation method for fitting the logistic regression model. We established a 10-gene CK signature (CKS) predictive of CK with high predictive accuracy (accuracy 94.22%; AUC 0.977). CKS was significantly associated with shorter overall survival in three independent cohorts, and was comparable to that of previously established risk stratification models for AML. Furthermore, we explored of therapeutic targets among the genes comprising CKS and identified the dysregulated expression of superoxide dismutase 1 (SOD1) gene, which is potentially amenable to SOD1 inhibitors.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据