Identification of the hub genes and pathways involved in acute myeloid leukemia using bioinformatics analysis

Tan, Youping; Zheng, Liling; Du, Yuanyuan; Zhong, Qi; Zhu, Yongjian; Li, Zhi; Liu, Shuang; Zhang, Qing

doi:10.1097/md.0000000000022047

Cited by 3 publications

(5 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Two encode for homeobox transcription factors ( EN1 , TLX3 ), and two other genes are involved in oxidative stress regulation ( NDUFAB1 , SPRR2A ). Further, an in-depth literature analysis revealed that several of these genes play important roles in cancer ( CDCA3 [ 26 ], ECEL1 [ 27 ], EN1 [ 28 ], HLA-DMB [ 29 , 30 ], SPRR2A [ 31 ], TMEM40 [ 32 , 33 , 34 ]) including acute myeloid leukemia ( CDCA3 [ 35 ], HLA-DMB [ 30 ], RPL18A [ 36 ], PF4 [ 37 , 38 ], PRG3 [ 39 ]) and T cell acute lymphoblastic leukemia ( TLX3 [ 40 ]). Moreover, some of these genes have already been reported to play a role in CML ( AURKB [ 41 ], AZU1 [ 42 , 43 ], HLA-B [ 44 ], HLA-DMB [ 30 ], PF4 [ 45 ]).…”

Section: Resultsmentioning

confidence: 99%

“…Moreover, two important drivers of other leukemias, PRG3 and TLX3 , were also among the 24 genes. PRG3 encodes a proteoglykane that has been reported as major regulator associated with survival of acute myeloid leukemia patients [ 39 ]. TLX3 encodes a homeobox transcription factor that is known as a master regulator of T cell acute lymphoblastic leukemia [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Comparative Gene Expression Analysis Reveals Similarities and Differences of Chronic Myeloid Leukemia Phases

Schwarz

Roeder

Seifert

2022

Cancers

View full text Add to dashboard Cite

Chronic myeloid leukemia (CML) is a slowly progressing blood cancer that primarily affects elderly people. Without successful treatment, CML progressively develops from the chronic phase through the accelerated phase to the blast crisis, and ultimately to death. Nowadays, the availability of targeted tyrosine kinase inhibitor (TKI) therapies has led to long-term disease control for the vast majority of patients. Nevertheless, there are still patients that do not respond well enough to TKI therapies and available targeted therapies are also less efficient for patients in accelerated phase or blast crises. Thus, a more detailed characterization of molecular alterations that distinguish the different CML phases is still very important. We performed an in-depth bioinformatics analysis of publicly available gene expression profiles of the three CML phases. Pairwise comparisons revealed many differentially expressed genes that formed a characteristic gene expression signature, which clearly distinguished the three CML phases. Signaling pathway expression patterns were very similar between the three phases but differed strongly in the number of affected genes, which increased with the phase. Still, significant alterations of MAPK, VEGF, PI3K-Akt, adherens junction and cytokine receptor interaction signaling distinguished specific phases. Our study also suggests that one can consider the phase-wise CML development as a three rather than a two-step process. This is in accordance with the phase-specific expression behavior of 24 potential major regulators that we predicted by a network-based approach. Several of these genes are known to be involved in the accumulation of additional mutations, alterations of immune responses, deregulation of signaling pathways or may have an impact on treatment response and survival. Importantly, some of these genes have already been reported in relation to CML (e.g., AURKB, AZU1, HLA-B, HLA-DMB, PF4) and others have been found to play important roles in different leukemias (e.g., CDCA3, RPL18A, PRG3, TLX3). In addition, increased expression of BCL2 in the accelerated and blast phase indicates that venetoclax could be a potential treatment option. Moreover, a characteristic signaling pathway signature with increased expression of cytokine and ECM receptor interaction pathway genes distinguished imatinib-resistant patients from each individual CML phase. Overall, our comparative analysis contributes to an in-depth molecular characterization of similarities and differences of the CML phases and provides hints for the identification of patients that may not profit from an imatinib therapy, which could support the development of additional treatment strategies.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Comparative Gene Expression Analysis Reveals Similarities and Differences of Chronic Myeloid Leukemia Phases

Schwarz

Roeder

Seifert

2022

Cancers

View full text Add to dashboard Cite

show abstract

“…The integration of bioinformatics tools with gene expression profiles has led to the prominent developments in cancer researche 33,34 . In recent years, several studies have investigated the relation of gene expression profile and hub genes in AML 35–37 . To the best of our knowledge, the current study is one of the few studies that analyzed the presence of IDRs in hub genes of AML.…”

Section: Discussionmentioning

confidence: 98%

“…33,34 In recent years, several studies have investigated the relation of gene expression profile and hub genes in AML. [35][36][37] To the best of our knowledge, the current study is one of the few studies that analyzed the presence of IDRs in hub genes of AML. Useful data can be achieved by constructing a PPI network of DEGs in specific cancer.…”

Section: Discussionmentioning

confidence: 99%

Identification of intrinsically disordered regions in hub genes of acute myeloid leukemia: A bioinformatics approach

Ameri

Alipour

Madihi

et al. 2021

Biotech and App Biochem

View full text Add to dashboard Cite

Acute myeloid leukemia (AML) is the most common acute leukemia in adults.Over the past decades, there has been a great challenge in the treatment of AML. A combination of gene expression profiling with computational approaches can lead to the identification of hub genes in AML. However, it is important to study the structure of these hub genes considering their importance in the proteinprotein interaction (PPI) network of specific cancer. In this study, we designed an integrated method to analyze the presence of intrinsically disordered regions (IDRs) in selected hub genes of AML. A gene expression profile of AML was obtained from Gene Expression Omnibus (GEO) database. Further analysis identified differentially expressed genes (DEGs) in AML. Additionally, the top 15 hub genes following construction and analysis of the PPI network of DEGs were selected. Validation of hub genes revealed that there is a reverse relationship between overexpression of FLT3, PPBP, and PF4 genes and the survival of AML patients. Based on IDRs investigation, FLT3 and PF4 are partially disordered, while PPBP is mostly disordered. Through clustering the network into structural modules, we identified two important modules in the PPI network of DEGs that showed the important position of PPBP in module 1. Based on further analysis of protein flexibility and its important role in biological processes, we suggest that PPBP can be considered as a potential drug target in AML. K E Y W O R D Sacute myeloid leukemia (AML), hub genes, intrinsically disordered regions (IDRs), PPI network Abbreviations: AML, Acute myeloid leukemia; PPI, protein-protein interaction; IDRs, intrinsically disordered regions; GEO, gene expression omnibus; DEGs, differentially expressed genes; BM, bone marrow; PB, peripheral blood; allo-HSCT, allogeneic hematopoietic stem cell transplantation; KEGG, kyoto encyclopedia of genes and genomes; GEPIA, gene expression profiling interactive analysis.

show abstract

“…Genetic mutations in cell proliferation, differentiation and apoptosis pathways are the basis for the pathogenesis of AML [ 3 , 4 ]. Mutation also results in abnormal gene expression of oncogenes or suppressor genes.…”

Section: Introductionmentioning

confidence: 99%

High FAAP24 expression reveals poor prognosis and an immunosuppressive microenvironment shaping in AML

et al. 2023

View full text Add to dashboard Cite

Background As a core member of the FA complex, in the Fanconi anemia pathway, FAAP24 plays an important role in DNA damage repair. However, the association between FAAP24 and patient prognosis in AML and immune infiltration remains unclear. The purpose of this study was to explore its expression characteristics, immune infiltration pattern, prognostic value and biological function using TCGA-AML and to verify it in the Beat AML cohort. Methods In this study, we examined the expression and prognostic value of FAAP24 across cancers using data from TCGA, TARGET, GTEx, and GEPIA2. To further investigate the prognosis in AML, development and validation of a nomogram containing FAAP24 were performed. GO/KEGG, ssGSEA, GSVA and xCell were utilized to explore the functional enrichment and immunological features of FAAP24 in AML. Drug sensitivity analysis used data from the CellMiner website, and the results were confirmed in vitro. Results Integrated analysis of the TCGA, TARGET and GTEx databases showed that FAAP24 is upregulated in AML; meanwhile, high FAAP24 expression was associated with poor prognosis according to GEPIA2. Gene set enrichment analysis revealed that FAAP24 is implicated in pathways involved in DNA damage repair, the cell cycle and cancer. Components of the immune microenvironment using xCell indicate that FAAP24 shapes an immunosuppressive tumor microenvironment (TME) in AML, which helps to promote AML progression. Drug sensitivity analysis showed a significant correlation between high FAAP24 expression and chelerythrine resistance. In conclusion, FAAP24 could serve as a novel prognostic biomarker and play an immunomodulatory role in AML. Conclusions In summary, FAAP24 is a promising prognostic biomarker in AML that requires further exploration and confirmation.

show abstract

Identification of the hub genes and pathways involved in acute myeloid leukemia using bioinformatics analysis

Abstract: Supplemental Digital Content is available in the text

Cited by 3 publications

References 28 publications

Comparative Gene Expression Analysis Reveals Similarities and Differences of Chronic Myeloid Leukemia Phases

Comparative Gene Expression Analysis Reveals Similarities and Differences of Chronic Myeloid Leukemia Phases

Identification of intrinsically disordered regions in hub genes of acute myeloid leukemia: A bioinformatics approach

High FAAP24 expression reveals poor prognosis and an immunosuppressive microenvironment shaping in AML

Contact Info

Product

Resources

About