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. 2023 Feb;45(1):53-63.
doi: 10.1111/ijlh.13963. Epub 2022 Sep 5.

High CX3CR1 expression predicts poor prognosis in paediatric acute myeloid leukaemia undergoing hyperleukocytosis

Nan Mei  1 , Hong Su  2 , Sha Gong  1 , Hanzhi Du  1 , Xiaojuan Zhang  1 , Lu Wang  1 , Huaiyu Wang  1
Affiliations

High CX3CR1 expression predicts poor prognosis in paediatric acute myeloid leukaemia undergoing hyperleukocytosis

Nan Mei et al. Int J Lab Hematol. 2023 Feb.

Abstract

Introduction: Paediatric AML patients with hyperleukocytosis have a poor prognosis and higher early mortality. Therefore, more studies are needed to explore relevant prognostic indicators and develop effective prevention strategies for this type of childhood AML.

Methods: All original data were obtained from the TARGET database. First, we explored meaningful differentially expressed genes (DEGs) between the hyperleukocytosis group and the non-hyperleukocytosis group. Next, we screened and identified valuable target genes using univariate Cox regression, Cytoscape software, and Kaplan-Meier survival curves. Finally, the coexpressed genes, functional networks, and immune-related activities associated with the target gene were deeply analysed by the GeneMANIA, LinkedOmics, GEPIA2021, TISIDB, and GSCA databases.

Results: We selected 1229 DEGs between the hyperleukocytosis group and the non-hyperleukocytosis group in paediatric AML patients. Among them, 495 DEGs were significantly linked with the overall survival of paediatric AML patients. Further, we discovered that CX3CR1 was a promising target gene. Meanwhile, we identified CX3CR1 as an independent prognostic predictor. Besides, we showed that CX3CR1 had strong physical interactions with CX3CL1. Additionally, functional network analysis suggested that CX3CR1 and its coexpressed genes modulated immune response pathways. Subsequent analysis found that immune cells with a high median value of CX3CR1 were monocytes, resting NK cells and CD8 T cells. Finally, we observed that CX3CR1 expression correlated with infiltrating levels of immune cells and immune signatures.

Conclusion: Elevated CX3CR1 expression may be an adverse prognostic indicator in paediatric AML patients undergoing hyperleukocytosis. Moreover, CX3CR1 may serve as an immunotherapeutic target for AML with hyperleukocytosis in children.

Keywords: CX3CR1; acute myeloid leukaemia; hyperleukocytosis; paediatric AML.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

FIGURE 1
FIGURE 1
PPI network construction, module analysis and hub gene identification by Cytoscape. Red nodes: upregulated DEGs; green nodes: downregulated DEGs. (A) PPI network of DEGs linked with the OS of paediatric AML patients (p < 0.05). (B) Six modules screened from the PPI network using MCODE. (C) Ten identified hub genes from the PPI network using MCC and MNC of CytoHubba
FIGURE 2
FIGURE 2
Prognostic value of hub genes for paediatric AML patients with hyperleukocytosis. Kaplan–Meier survival analysis for OS. (A) CD1A; (B) CD1B; (C) CD1C; (D) CX3CR1; (E) CSF2; (F) CCL2; (G) CD5; (H) CD8A; (I) CXCL1; (J) CXCL11
FIGURE 3
FIGURE 3
Analyses of genes that interact and are coexpressed with CX3CR1. (A) Interactive genes with CX3CR1 according to GeneMANIA. (B) The overall CX3CR1 highly correlated genes identified by Pearson's test in AML according to LinkedOmics. (C) Heatmap of the top 50 significant genes positively correlated with CX3CR1 in AML. (D) Heatmap of the top 50 significant genes negatively correlated with CX3CR1 in AML
FIGURE 4
FIGURE 4
(A) CX3CR1 gene expression in various immune cells by CIBERSORT (GEPIA2021). (B) The association between immune cell infiltrates and GSVA score in AML. *p < 0.05; # FDR ≤ 0.05
FIGURE 5
FIGURE 5
Spearman correlations between CX3CR1 and immune‐related genes across cancers in TISIDB. (A) Spearman correlations between CX3CR1 and chemokines. (B) Spearman correlations between CX3CR1 and immune inhibitors. (C) Spearman correlations between CX3CR1 and immune stimulators. (D) Spearman correlations between CX3CR1 and lymphocytes. (E) Spearman correlations between CX3CR1 and MHC molecules. (F) Spearman correlations between CX3CR1 and chemokine receptors
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