Journal of Shanghai Jiao Tong University (Medical Science) >

2021 , Vol. 41 >Issue 5: 579 - 587

DOI: https://doi.org/10.3969/j.issn.1674-8115.2021.05.004

Basic research

Analysis of tumor immune-related differentially expressed genes in adults and children with acute myeloid leukemia

  • Ling-ling LI ,
  • Qian LI ,
  • Ming-yu LI ,
  • Zheng LIU ,
  • Qian-cheng SHEN
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  • 1.Department of Central Laboratory, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai 200062, China
    2.Medicinal Bioinformatics Center, Shanghai Jiao Tong University College of Basic Medical Sciences, Shanghai 200025, China
    3.School of Management, Shanghai University of Engineering Science, Shanghai 201620, China

Online published: 2021-05-27

Supported by

Youth Project of Shanghai Municipal Commission of Health and Family Planning(20184Y0220)

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Abstract

Objective

·To analyze tumor immune-related differentially expressed genes (DEGs) in the bone marrow of adults and children with acute myeloid leukemia (AML).

Methods

·The GSE134589 data set was downloaded from the GEO (Gene Expression Omnibus) database, and the patients in initial diagnosis/relapse were selected and divided into children group (0?16 years old, 34 cases), young and middle-aged group (17?59 years old, 62 cases) and elders group (60?80 years old, 62 cases). The tumor immune-related DEGs in the bone marrow samples of different groups of patients were screened by R language packages. The common DEGs of young and middle-aged group vs children group and elders group vs children group were compared with the DEGs of adults group vs children group in complete remission, and the functional enrichment analysis was conducted with the common DEGs. The Kaplan-Meier method was used to screen the DEGs that were significantly related to prognosis, and the core regulatory DEGs were screened by constructing a protein-protein interaction (PPI) network. The genes screened by the above two methods were regarded as key genes. The expression levels of the key genes in AML, diffuse large B cell lymphoma (DLBCL) and thymoma tumor samples and normal human samples were compared by GEPIA server, and the mRNA expression levels of key genes in the human AML tumor stem cells and the original hematopoietic cells of healthy people were analyzed by GEXC website.

Results

·In the GSE134589 data set, there were 51 DEGs up-regulated and 21 down-regulated between the young and middle-aged group and the children group; 47 DEGs were up-regulated and 20 down-regulated between the elders group and the children group; no DEG was found between the young and middle-aged group and the elders group. Fifty-seven tumor immune-related DEGs were screened in both the young and middle-aged group and the elders group, of which 39 were up-regulated and 18 were down-regulated; in these DEGs only 3 genes showed statistically significant difference in expression level when the disease was incomplete remission. The 57 common DEGs were mainly enriched in leukocyte migration and cytokine-related signal pathways. The patients with high expression of interleukin-2 receptor subunit alpha (IL2RA) and FMS-like tyrosine kinase 3 (FLT3) had significantly shorter overall survival than those with low expression (both P<0.05), and complement component 3a receptor 1 (C3AR1) was the core regulatory gene of the PPI network. The three DEGs were selected as key genes. They were all specifically highly expressed in the AML tumor samples (all P<0.05), and IL2RA was also significantly highly expressed in the DLBCL samples (P<0.05). The expression level of IL2RA was low both in the AML tumor stem cells and the original group of hematopoietic cells, but FLT3 was highly expressed in these cells. The expression level of C3AR1 was specifically high in the AML tumor stem cells.

Conclusion

·The difference in the prognosis between adults and children with AML may be related to the differences in the expression of tumor immune-related genes in bone marrow, in which IL2RA, FLT3 and C3AR1 may be the key genes.

Key words： acute myeloid leukemia (AML); tumor immunity; differentially expressed gene (DEG); interleukin-2 receptor subunit alpha (IL2RA); FMS-like tyrosine kinase 3 (FLT3); complement component 3a receptor 1 (C3AR1)

Cite this article

Ling-ling LI , Qian LI , Ming-yu LI , Zheng LIU , Qian-cheng SHEN . Analysis of tumor immune-related differentially expressed genes in adults and children with acute myeloid leukemia[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2021 , 41(5) : 579 -587 . DOI: 10.3969/j.issn.1674-8115.2021.05.004

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