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. 2022 Nov 29;22(1):1229.
doi: 10.1186/s12885-022-10352-6.

Comprehensive analysis of ID genes reveals the clinical and prognostic value of ID3 expression in acute myeloid leukemia using bioinformatics identification and experimental validation

Qi Zhao #  1   2   3   4   5 , Yun Wang #  1   2   3 , Di Yu #  1   2   3 , Jia-Yan Leng  1   2   3 , Yangjing Zhao  6 , Mingqiang Chu  2   3   4   5 , Zijun Xu  2   3   4 , Hao Ding  7 , Jingdong Zhou  8   9   10 , Tingjuan Zhang  11   12   13
Affiliations

Comprehensive analysis of ID genes reveals the clinical and prognostic value of ID3 expression in acute myeloid leukemia using bioinformatics identification and experimental validation

Qi Zhao et al. BMC Cancer. .

Abstract

Background: Dysregulation of inhibitor of differentiation/DNA binding (ID) genes is linked to cancer growth, angiogenesis, invasiveness, metastasis and patient survival. Nevertheless, few investigations have systematically determined the expression and prognostic value of ID genes in acute myeloid leukemia (AML).

Methods: The expression and clinical prognostic value of ID genes in AML were first identified by public databases and further validated by our research cohort.

Results: Using public data, the expression of ID1/ID3 was markedly downregulated in AML, and the expression of ID2 was greatly upregulated in AML, whereas ID4 showed no significant difference. Among the ID genes, only ID3 expression may be the most valuable prognostic biomarker in both total AML and cytogenetically normal AML (CN-AML) and especially in CN-AML. Clinically, reduced ID3 expression was greatly associated with higher white blood cell counts, peripheral blood/bone marrow blasts, normal karyotypes and intermediate cytogenetic risk. In addition, low ID3 expression was markedly related to FLT3 and NPM1 mutations as well as wild-type TP53. Despite these associations, multivariate Cox regression analysis revealed that ID3 expression was an independent risk factor affecting overall survival (OS) and disease free survival (DFS) in CN-AML patients. Biologically, a total of 839 mRNAs/lncRNAs and 72 microRNAs were found to be associated with ID3 expression in AML. Importantly, the expression of ID3 with discriminative value in AML was further confirmed in our research cohort.

Conclusion: The bioinformatics analysis and experimental verification demonstrate that low ID3 expression independently affects OS and DFS in patients with CN-AML, which might be seen as a potential prognostic indicator in CN-AML.

Keywords: AML; Expression; ID; ID3; Prognosis.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Expression of ID genes in AML. a ID1 expression in AML; b ID2 expression in AML; c ID3 expression in AML; d ID4 expression in AML. *: P < 0.001. The expression of ID genes expression in AML compared with controls is analyzed in GEPIA (http://gepia.cancer-pku.cn/)
Fig. 2
Fig. 2
Prognostic value of ID genes in AML. The prognostic effect of ID genes (ID1/ID2/ID3/ID4) on overall survival and disease free survival were analyzed by Kaplan–Meier method
Fig. 3
Fig. 3
The associations of ID3 expression with cytogenetic risks/genetic abnormalities in AML. a ID3 expression among different cytogenetic risks of AML. b ID3 expression in AML patients with and without FLT3 mutations. c ID3 expression in AML patients with and without NPM1 mutations. d ID3 expression in AML patients with and without CEBPA mutations. e ID3 expression in AML patients with and without TP53 mutations
Fig. 4
Fig. 4
Biological network of aberrant ID3 expression in AML. a Expression heatmap of differentially expressed mRNAs/lncRNAs between low and high ID3 expression groups in AML (|log2 FC|>1.5, FDR < 0.05 and P < 0.05). b Volcano plot of differentially expressed mRNAs/lncRNAs between low and high ID3 expression groups in AML. c Gene Ontology (GO) analysis of differentially expressed mRNAs/lncRNAs. d Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of differentially expressed mRNAs/lncRNAs. e Expression heatmap of differentially expressed miRNAs between low and high ID3 expression groups in AML (FDR < 0.05 and P < 0.05)
Fig. 5
Fig. 5
Validation of ID3 expression and its discriminative capacity in AML. a The relative expression of ID3 in AML. b ROC curve analysis of ID3 expression in distinguishing AML controls
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