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. 2017 Jan 3;8(1):1529-1540.
doi: 10.18632/oncotarget.13650.

Association of a cytarabine chemosensitivity related gene expression signature with survival in cytogenetically normal acute myeloid leukemia

Han Yan  1   2   3 , Lu Wen  4 , Dan Tan  1   2   3 , Pan Xie  1   2   3 , Feng-Mei Pang  1   2   3 , Hong-Hao Zhou  1   2   3 , Wei Zhang  1   2   3 , Zhao-Qian Liu  1   2   3 , Jie Tang  1   2   3 , Xi Li  1   2   3 , Xiao-Ping Chen  1   2   3
Affiliations

Association of a cytarabine chemosensitivity related gene expression signature with survival in cytogenetically normal acute myeloid leukemia

Han Yan et al. Oncotarget. .

Abstract

The prognosis of cytogenetically normal acute myeloid leukemia (CN-AML) varies greatly among patients. Achievement of complete remission (CR) after chemotherapy is indispensable for a better prognosis. To develop a gene signature predicting overall survival (OS) in CN-AML, we performed data mining procedure based on whole genome expression data of both blood cancer cell lines and AML patients from open access database. A gene expression signature including 42 probes was derived. These probes were significantly associated with both cytarabine half maximal inhibitory concentration values in blood cancer cell lines and OS in CN-AML patients. By using cox regression analysis and linear regression analysis, a chemo-sensitive score calculated algorithm based on mRNA expression levels of the 42 probes was established. The scores were associated with OS in both the training sample (p=5.13 × 10-4, HR=2.040, 95% CI: 1.364-3.051) and the validation sample (p=0.002, HR=2.528, 95% CI: 1.393-4.591) of the GSE12417 dataset from Gene Expression Omnibus. In The Cancer Genome Atlas (TCGA) CN-AML patients, higher scores were found to be associated with both worse OS (p=0.013, HR=2.442, 95% CI: 1.205-4.950) and DFS (p=0.015, HR=2.376, 95% CI: 1.181-4.779). Results of gene ontology (GO) analysis showed that all the significant GO Terms were correlated with cellular component of mitochondrion. In summary, a novel gene set that could predict prognosis of CN-AML was identified presently, which provided a new way to identify genes impacting AML chemo-sensitivity and prognosis.

Keywords: acute myeloid leukemia; chemosensitivity; cytarabine; prognosis; signature.

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Conflict of interest statement

CONFLICTS OF INTEREST

The authors declare that they have no competing interests.

Figures

Figure 1
Figure 1. Whole genome expression pattern impact cytarabine sensitivity in blood cancer cell lines
A. Cluster analysis of all probes in blood cancer cell lines, B. Comparison of cytarabine IC50 values between two classes of blood cancer cell lines divided by cluster analysis.
Figure 2
Figure 2. GO and KEGG pathway analysis of genes notably impacting cytarabine IC50 in blood cancer cell lines
The top ten significantly enriched GO categories and pathways were calculated and plotted as the − 1 × log10 (p value). A. Biological process, B. Molecular function, C. Cellular component, D. KEGG Pathways.
Figure 3
Figure 3. Survival curve of AML patients stratified by chemo-sensitivity score
A. U133 AB samples; B. U133 plus samples.
Figure 4
Figure 4. Influence of chemo-sensitivity score on OS and DFS of CN-AML in TCGA AML dataset
Figure 5
Figure 5. Methods flow chart of analysis process
See this image and copyright information in PMC

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