Identification of a Complex Karyotype Signature with Clinical Implications in AML and MDS-EB Using Gene Expression Profiling
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 exp...
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| Format: | Article |
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MDPI AG
2023-11-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/15/21/5289 |
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| author | Cheonghwa Lee Ha Nui Kim Jung Ah Kwon Jinha Hwang Ji-Ye Park Ok Sarah Shin Soo-Young Yoon Jung Yoon |
| author_facet | Cheonghwa Lee Ha Nui Kim Jung Ah Kwon Jinha Hwang Ji-Ye Park Ok Sarah Shin Soo-Young Yoon Jung Yoon |
| author_sort | Cheonghwa Lee |
| collection | DOAJ |
| description | 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 (<i>SOD1</i>) gene, which is potentially amenable to SOD1 inhibitors. |
| first_indexed | 2024-03-11T11:32:30Z |
| format | Article |
| id | doaj.art-45e83b1e92f14046a9b35c940116cec0 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-11T11:32:30Z |
| publishDate | 2023-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-45e83b1e92f14046a9b35c940116cec02023-11-10T15:00:31ZengMDPI AGCancers2072-66942023-11-011521528910.3390/cancers15215289Identification of a Complex Karyotype Signature with Clinical Implications in AML and MDS-EB Using Gene Expression ProfilingCheonghwa Lee0Ha Nui Kim1Jung Ah Kwon2Jinha Hwang3Ji-Ye Park4Ok Sarah Shin5Soo-Young Yoon6Jung Yoon7Department of Laboratory Medicine, College of Medicine, Korea University, Seoul 08308, Republic of KoreaDepartment of Laboratory Medicine, College of Medicine, Korea University, Seoul 08308, Republic of KoreaDepartment of Laboratory Medicine, College of Medicine, Korea University, Seoul 08308, Republic of KoreaDepartment of Laboratory Medicine, College of Medicine, Korea University, Seoul 08308, Republic of KoreaBK21 Graduate Program, Department of Biomedical Sciences, College of Medicine, Korea University Guro Hospital, Seoul 08308, Republic of KoreaBK21 Graduate Program, Department of Biomedical Sciences, College of Medicine, Korea University Guro Hospital, Seoul 08308, Republic of KoreaDepartment of Laboratory Medicine, College of Medicine, Korea University, Seoul 08308, Republic of KoreaDepartment of Laboratory Medicine, College of Medicine, Korea University, Seoul 08308, Republic of KoreaComplex 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 (<i>SOD1</i>) gene, which is potentially amenable to SOD1 inhibitors.https://www.mdpi.com/2072-6694/15/21/5289complex karyotypeAMLMDSgene expressionSOD1 |
| spellingShingle | Cheonghwa Lee Ha Nui Kim Jung Ah Kwon Jinha Hwang Ji-Ye Park Ok Sarah Shin Soo-Young Yoon Jung Yoon Identification of a Complex Karyotype Signature with Clinical Implications in AML and MDS-EB Using Gene Expression Profiling Cancers complex karyotype AML MDS gene expression SOD1 |
| title | Identification of a Complex Karyotype Signature with Clinical Implications in AML and MDS-EB Using Gene Expression Profiling |
| title_full | Identification of a Complex Karyotype Signature with Clinical Implications in AML and MDS-EB Using Gene Expression Profiling |
| title_fullStr | Identification of a Complex Karyotype Signature with Clinical Implications in AML and MDS-EB Using Gene Expression Profiling |
| title_full_unstemmed | Identification of a Complex Karyotype Signature with Clinical Implications in AML and MDS-EB Using Gene Expression Profiling |
| title_short | Identification of a Complex Karyotype Signature with Clinical Implications in AML and MDS-EB Using Gene Expression Profiling |
| title_sort | identification of a complex karyotype signature with clinical implications in aml and mds eb using gene expression profiling |
| topic | complex karyotype AML MDS gene expression SOD1 |
| url | https://www.mdpi.com/2072-6694/15/21/5289 |
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