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. 2023 May 27;16(1):117.
doi: 10.1186/s12920-023-01550-7.

Comprehensive bioinformatic analysis of the expression and prognostic significance of TSC22D domain family genes in adult acute myeloid leukemia

XiaoQiang Xu #  1   2 , Rui Sun #  3 , YuanZhang Li #  1 , JiaXi Wang  1 , Meng Zhang  1 , Xia Xiong  1 , DanNi Xie  1 , Xin Jin  4 , MingFeng Zhao  5
Affiliations

Comprehensive bioinformatic analysis of the expression and prognostic significance of TSC22D domain family genes in adult acute myeloid leukemia

XiaoQiang Xu et al. BMC Med Genomics. .

Abstract

Background: TSC22D domain family genes, including TSC22D1-4, play a principal role in cancer progression. However, their expression profiles and prognostic significance in adult acute myeloid leukemia (AML) remain unknown.

Methods: The online databases, including HPA, CCLE, EMBL-EBI, GEPIA2, BloodSpot, GENT2, UCSCXenaShiny, GSCALite, cBioportal, and GenomicScape, utilized the data of TCGA and GEO to investigate gene expression, mutation, copy number variation (CNV), and prognostic significance of the TSC22D domain family in adult AML. Computational analysis of resistance (CARE) was used to explore the effect of TSC22D3 expression on drug response. Functional enrichment analysis of TSC22D3 was performed in the TRRUST Version 2 database. The STRING, Pathway Commons, and AnimalTFDB3.0 databases were used to investigate the protein-protein interaction (PPI) network of TSC22D3. Harmonizome was used to predict target genes and kinases regulated by TSC22D3. The StarBase v2.0 and CancermiRNome databases were used to predict miRNAs regulated by TSC22D3. UCSCXenaShiny was used to investigate the correlation between TSC22D3 expression and immune infiltration.

Results: Compared with normal adult hematopoietic stem cells (HSCs), the expression of TSC22D3 and TSC22D4 in adult AML tissues was markedly up-regulated, whereas TSC22D1 expression was markedly down-regulated. The expression of TSC22D1 and TSC22D3 was significantly increased in adult AML tissues compared to normal adult tissues. High TSC22D3 expression was significantly associated with poor overall survival (OS) and event-free survival (EFS) in adult AML patients. Univariate and multivariate Cox analysis showed that overexpression of TSC22D3 was independently associated with adverse OS of adult AML patients. High TSC22D3 expression had a adverse impact on OS and EFS of adult AML patients in the chemotherapy group. TSC22D3 expression correlated with drug resistance to BCL2 inhibitors. Functional enrichment analysis indicated that TSC22D3 might promote AML progression. MIR143-3p sponging TSC22D3 might have anti-leukemia effect in adult AML.

Conclusions: A significant increase in TSC22D3 expression was observed in adult AML tissues compared to normal adult HSCs and tissues. The prognosis of adult AML patients with high TSC22D3 expression was unfavorable, which could severe as a new prognostic biomarker and potential target for adult AML.

Keywords: Acute myeloid leukemia; Drug response; Prognostic biomarker; Tumor infiltration.

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Conflict of interest statement

TCGA and GEO belong to public databases. The patients involved in the database have obtained ethical approval. Users can download relevant data for free for research and publish relevant articles. Our study is based on open source data, so there are no ethical issues and other conflicts of interest.

All authors declare that there are no competing interests.

Figures

Fig. 1
Fig. 1
Flow chart of the present study
Fig. 2
Fig. 2
Gene expression of the TSC22D domain family in AML cell lines. A Bar graphs of the expression of the TSC22D domain family genes in 88 leukemia cell lines (including 38 AML cell lines) in the HPA database. The height of the bar charts represented the level of gene expression. B Heatmap of the expression of the TSC22D domain family genes in 43 AML cell lines in the CCLE database. The color of the Heatmap represented the level of gene expression. C Bar chart of the expression of the TSC22D domain family genes in 16 AML cell lines in the EMBL-EBI database. The shade of color in the bar graphs indicated the level of gene expression
Fig. 3
Fig. 3
Gene expression of the TSC22D domain family in AML tissues and CD34 positive HSCs from normal adult bone marrow tissues was measured and compared using the Wilcoxon rank-sum test (*P < 0.05,**P < 0.01,***P < 0.001,****P < 0.0001, ns means no statistical significance). A The expression of TSC22D family genes in 252 AML tissues and 6 CD34 positive HSCs from normal adult bone marrow tissues was measured using the “ Normal hematopoiesis with AMLs” dataset of the Bloodspot database. B The expression of TSC22D family genes in 1825 AML tissues and 6 CD34 positive HSCs from normal adult bone marrow tissues was measured using the “ BloodPool: AML samples with normal cells” dataset of the Bloodspot database. C The expression of TSC22D family genes in 2802 AML tissues and 17 CD34 positive HSCs from normal adult bone marrow tissues was measured using the GPL570 platform (HG-U133_Plus_2) of the GENT2 database
Fig. 4
Fig. 4
The expression of the TSC22D domain family genes in adult AML tissues and normal adult tissues was measured and compared using the Wilcoxon rank-sum test (*P < 0.05,**P < 0.01,***P < 0.001,****P < 0.0001, ns means no statistical significance). A The expression of the TSC22D domain family genes in 173 TCGA-LAML tissues and 70 GTEx-normal tissues using the GEPIA2 database. B The expression of the TSC22D domain family genes in 542 adult AML tissues and 73 normal adult bone marrow tissues using the Leukemia MILE study dataset of the Bloodspot database. C The expression of the TSC22D domain family genes in 2802 adult AML tissues and 134 normal adult bone marrow tissues using the GENT2 database
Fig. 5
Fig. 5
The effect of TSC22D3 expression on AML. A The effect of TSC22D3 expression on OS of 173 adult AML patients. B The effect of TSC22D3 expression on OS of 100 adult AML patients in the chemotherapy group. C The effect of TSC22D3 expression on OS of 73 adult AML patients in the transplantation group. D The effect of TSC22D3 expression on EFS of 171 adult AML patients. E The effect of TSC22D3 expression on EFS of 98 adult AML patients in the chemotherapy group. F The effect of TSC22D3 expression on EFS of 73 adult AML patients in the transplantation group. G The effect of TSC22D3 expression on drug response using the CGP dataset of the CARE database. H The effect of TSC22D3 expression on drug response using the CTRP dataset of the CARE database
Fig. 6
Fig. 6
The profiles of gene mutation and CNV of TSC22D3 in adult AML and its effect on OS of adult AML patients. A Gene mutation rate of TSC22D3 in 165 adult AML samples using the TCGA PanCancer Atlas dataset of the cBioportal database. B The CNV of TSC22D3 in 179 adult AML samples using the GSCALite database. C The effect of gene mutation of TSC22D3 on OS of 165 adult AML patients using the cBioportal database. D The effect of CNV of TSC22D3 on OS of 179 adult AML patients using the GSCALite database
Fig. 7
Fig. 7
Functional enrichment analysis and PPI analysis of TSC22D3. A Gene ontology biological process, diseases ontology, and KEGG pathway of TSC22D3 using the TRRUST Version 2 database. B PPI analysis of TSC22D3 using the String database. C PPI analysis of TSC22D3 using the Pathway Commons database. D PPI analysis of TSC22D3 using the AnimalTFDB3.0 database. E The expression of FOS in 173 TCGA-LAML and 70 GTEx-Normal using the UCSCXenaShiny database. F The correlation between TSC22D3 and FOS using the UCSCXenaShiny database. G The effect of FOS expression on OS of adult AML patients using the GenomicScape database
Fig. 8
Fig. 8
Predicted target genes and kinases regulated by TSC22D3. A The target genes regulated by TSC22D3 using the Harmonizome database. B The expression of CREB1 in 173 TCGA-LAML tissues and 70 GTEx-Normal tissues using the UCSCXenaShiny database. C The correlation between TSC22D3 and CREB1 using the UCSCXenaShiny database. D The effect of CREB1 expression on OS of 162 adult AML patients using the GenomicScape database. E Top 20 kinases regulated by TSC22D3 using the Harmonizome database. F The expression of predicted kinases in 173 TCGA-LAML tissues and 70 GTEx-Normal tissues using the UCSCXenaShiny database. G The correlation between TSC22D3 and predicted kinases using the UCSCXenaShiny database. H The effect of TSC22D3 regulated kinases on OS of 161 adult AML patients using the UCSCXenaShiny database
Fig. 9
Fig. 9
Analysis of miRNAs regulated by TSC22D3. A Predicted miRNAs regulated by TSC22D3 using the StarBase v2.0 database. B The correlation between TSC22D3 and MIR143-3p in 83 adult AML samples using the StarBase v2.0 database. C The correlation between TSC22D3 and MIR143-3p in 173 adult AML samples using the UCSCXenaShiny database. D The effect of MIR143-3p expression on OS of 161 adult AML patients using the UCSCXenaShiny database. E The effect of MIR143-3p expression on OS of 188 adult AML patients using the CancermiRNome database. F Diseases ontology of MIR143-3p using the CancermiRNome database. G KEGG pathways of MIR143-3p using the CancermiRNome database
Fig. 10
Fig. 10
The correlation between TSC22D3 expression and immune cell infiltration in adult AML using the UCSCXenaShiny database. A CIBERSORT B QUANTISEQ C MCPCOUNTER D EPIC E XCELL
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