Open Access

Genome-scale integrated analysis to identify prospective molecular mechanisms and therapeutic targets in isocitrate dehydrogenase 2 R140Q-mutated acute myeloid leukemia

  • Authors:
    • Rui Huang
    • Xiwen Liao
    • Jing Li
    • Jiemin Wei
    • Xiayun Su
    • Xiaoxuan Lai
    • Beicai Liu
    • Fangxiao Zhu
    • Yumei Huang
    • Qiaochuan Li
  • View Affiliations

  • Published online on: March 18, 2019     https://doi.org/10.3892/or.2019.7075
  • Pages: 2876-2888
  • Copyright: © Huang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The aim of the present study was to identify potential molecular mechanisms and therapeutic targets in regards to isocitrate dehydrogenase 2 (IDH2) R140Q-mutated acute myeloid leukemia (AML). An RNA sequencing dataset of IDH2 wild-type and R140Q-mutated adult de novo AML bone marrow samples was obtained from The Cancer Genome Atlas (TCGA) database. The edgeR package was used to screen for the differentially expressed genes (DEGs), and the potential molecular mechanisms and therapeutic targets were identified using Database for Annotation, Visualization, and Integrated Discovery (DAVID) v6.8, Biological Networks Gene Ontology tool, Connectivity Map (CMap), Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) and GeneMANIA. A total of 230 DEGs were identified between the bone marrow tissues of IDH2 R140Q-mutated and wild-type AML patients, of which 31 were significantly associated with overall survival (OS). Functional assessment of DEGs showed significant enrichment in multiple biological processes, including angiogenesis and cell differentiation. STRING and GeneMANIA were used to identify the hub genes of these DEGs. CMap analysis identified 13 potential small-molecule drugs against IDH2 R140Q-mutated adult de novo AML. Genome-wide co-expression network analysis identified several IDH2 R140Q co-expressed genes, of which 56 were significantly associated with AML OS. The difference in IDH2 mRNA expression levels and OS between the IDH2 R140Q-mutated and wild-type AML were not statistically significant in our cohort. In conclusion, we identified several co-expressing genes and potential molecular mechanisms that are instrumental in IDH2 R140Q-mutated adult de novo AML, along with 13 candidate targeted therapeutic drugs.
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May-2019
Volume 41 Issue 5

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Copy and paste a formatted citation
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Spandidos Publications style
Huang R, Liao X, Li J, Wei J, Su X, Lai X, Liu B, Zhu F, Huang Y, Li Q, Li Q, et al: Genome-scale integrated analysis to identify prospective molecular mechanisms and therapeutic targets in isocitrate dehydrogenase 2 R140Q-mutated acute myeloid leukemia. Oncol Rep 41: 2876-2888, 2019
APA
Huang, R., Liao, X., Li, J., Wei, J., Su, X., Lai, X. ... Li, Q. (2019). Genome-scale integrated analysis to identify prospective molecular mechanisms and therapeutic targets in isocitrate dehydrogenase 2 R140Q-mutated acute myeloid leukemia. Oncology Reports, 41, 2876-2888. https://doi.org/10.3892/or.2019.7075
MLA
Huang, R., Liao, X., Li, J., Wei, J., Su, X., Lai, X., Liu, B., Zhu, F., Huang, Y., Li, Q."Genome-scale integrated analysis to identify prospective molecular mechanisms and therapeutic targets in isocitrate dehydrogenase 2 R140Q-mutated acute myeloid leukemia". Oncology Reports 41.5 (2019): 2876-2888.
Chicago
Huang, R., Liao, X., Li, J., Wei, J., Su, X., Lai, X., Liu, B., Zhu, F., Huang, Y., Li, Q."Genome-scale integrated analysis to identify prospective molecular mechanisms and therapeutic targets in isocitrate dehydrogenase 2 R140Q-mutated acute myeloid leukemia". Oncology Reports 41, no. 5 (2019): 2876-2888. https://doi.org/10.3892/or.2019.7075