Identification and validation of inferior prognostic genes associated with immune signatures and chemotherapy outcome in acute myeloid leukemia.

Szczegóły
Abstrakt

Tytuł:: Identification and validation of inferior prognostic genes associated with immune signatures and chemotherapy outcome in acute myeloid leukemia.
Autorzy:: Wang J; School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 211198, China.; Department of Pharmacy, First Affiliated Hospital of Xinjiang Medical University, Urumqi 830011, China.
Hao JP; Department of Hematology, First Affiliated Hospital of Xinjiang Medical University, Urumqi 830011, China.
Uddin MN; School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 211198, China.
Wu Y; Department of General Medicine, First Affiliated Hospital of Xinjiang Medical University, Urumqi 830011, China.
Chen R; Department of Hematology, First Affiliated Hospital of Xinjiang Medical University, Urumqi 830011, China.
Li DF; Department of Pharmacy, First Affiliated Hospital of Xinjiang Medical University, Urumqi 830011, China.
Xiong DQ; Department of Pharmacy, First Affiliated Hospital of Xinjiang Medical University, Urumqi 830011, China.
Ding N; Department of Pharmacy, First Affiliated Hospital of Xinjiang Medical University, Urumqi 830011, China.
Yang JH; Department of Pharmacy, First Affiliated Hospital of Xinjiang Medical University, Urumqi 830011, China.
Ding XS; School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 211198, China.
Źródło:: Aging [Aging (Albany NY)] 2021 Jun 18; Vol. 13 (12), pp. 16445-16470. Date of Electronic Publication: 2021 Jun 18.
Typ publikacji:: Journal Article; Research Support, Non-U.S. Gov't
Język:: English
Imprint Name(s):: Original Publication: Albany, NY : Impact Journals, LLC
MeSH Terms:: Gene Expression Profiling*
Gene Expression Regulation, Leukemic*
Leukemia, Myeloid, Acute/*genetics
Leukemia, Myeloid, Acute/*immunology
Female ; Gene Ontology ; Gene Regulatory Networks ; Genes, Essential ; Humans ; Leukemia, Myeloid, Acute/drug therapy ; Male ; Middle Aged ; Prognosis ; Protein Interaction Maps/genetics ; RNA, Long Noncoding/genetics ; RNA, Long Noncoding/metabolism ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; ROC Curve ; Reproducibility of Results ; Signal Transduction/genetics ; Transcriptome/genetics ; Treatment Outcome ; Tumor Microenvironment/genetics
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Contributed Indexing:: Keywords: acute myeloid leukaemia; immune infiltration; key genes; survival prognosis; weighted gene co-expression network analysis
Substance Nomenclature:: 0 (RNA, Long Noncoding)
0 (RNA, Messenger)
Entry Date(s):: Date Created: 20210620 Date Completed: 20210720 Latest Revision: 20210720
Update Code:: 20240104
PubMed Central ID:: PMC8266366
DOI:: 10.18632/aging.203166
PMID:: 34148032
: Czasopismo naukowe

Acute myeloid leukemia (AML) is a group of heterogeneous hematological malignancies. We identified key genes as ITGAM and lncRNA ITGB2-AS1 through different bioinformatics tools. Furthermore, qPCR was performed to verify the expression level of essential genes in clinical samples. Retrospective research on 179 AML cases was used to investigate the relationship between the expression of ITGAM and the characteristics of AML. The critical gene relationship with immune infiltration in AML was estimated. The clinical validation and prognostic investigation showed that ITGAM , PPBP , and ITGB2-AS1 are highly expressed in AML ( P < 0.001) and significantly associated with the overall survival in AML. Moreover, the retrospective research on 179 clinical cases showed that positive expression of ITGAM is substantially related to AML classification ( P < 0.001), higher count of white blood cells ( P < 0.01), and poor chemotherapy outcome ( P < 0.05). Furthermore, based on grouping ITGAM as the high and low expression in TCGA-LAML profile, we found that genes in the highly expressed ITGAM group are mainly involved in immune infiltration and inflammation-related signaling pathways. Finally, we discovered that the expression level of ITGAM and lncRNA ITGB2-AS1 are not just closely related to the immune score and stromal score ( P < 0.001) but also significantly positively correlated with various Immune signatures in AML ( P < 0.001), indicating the association of these genes with immunosuppression in AML. The prediction of candidate drugs indicated that certain immunosuppressive drugs have potential therapeutic effects for AML. The critical genes could be used as potential biomarkers to evaluate the survival and prognosis of AML.

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