Abstract

Background The tumor microenvironment (TME) plays a significant role in the progression and prognosis of acute myeloid leukemia (AML). This study is aimed at exploring TME-associated biomarkers and identify their potential mechanism in the microenvironment of AML. Method In this study, the stromal, immune, and ESTIMATE scores of AML patients were evaluated with the ESTIMATE and CIBERSORT algorithms; then, the AML samples were divided into high- and low-score groups. We evaluated the association between clinicopathological characteristics, survival rate, and the stromal/immune/ESTIMATE scores. Furthermore, we identified TME-associated differentially expressed genes (DEGs) then carried out pathway enrichment analysis, protein-protein interaction (PPI) network, Cox regression analysis, and Kaplan-Meier survival analysis to select the most crucial genes. In addition, we further explored the potential mechanism of HCK in the AML microenvironment. Results We identified 624 TME-associated DEGs and found that HCK was the most promising biomarker associated with AML. The results of the gene set enrichment analysis (GSEA) indicated that HCK was mainly involved in immune and inflammation-related signaling pathways. In addition, CIBERSORT analysis showed that HCK was closely related to tumor immune infiltration, with HCK expression associated with various infiltrating immune cells, including B cells, T cells, tumor-associated macrophages (TAM), NK cells, plasma cells, eosinophils, and neutrophils. Furthermore, HCK expression was closely related with ELN risk stratification in patients with AML. Conclusion HCK could regulate immune cell infiltration in the microenvironment of AML and may act as a potential biomarker for the treatment and prognosis of AML patients.

Highlights

  • Acute myeloid leukemia (AML) is a highly heterogeneous hematological malignancy, which is the most common type of acute leukemia in adults [1]

  • We identified tumor microenvironment (TME)-associated differentially expressed genes (DEG) carried out pathway enrichment analysis, protein-protein interaction (PPI) network analysis, Cox regression analysis, and Kaplan-Meier survival analysis to select the most crucial genes

  • We further explored the possible mechanism of HCK expression in TME, and correlation analysis between HCK expression and the tumorinfiltrating immune cells (TIICs) was performed

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Summary

Introduction

Acute myeloid leukemia (AML) is a highly heterogeneous hematological malignancy, which is the most common type of acute leukemia in adults [1]. Identifying potential biomarkers will contribute to the diagnosis, treatment, and prognosis of patients with AML. The tumor microenvironment (TME) has been considered a crucial factor for the diagnosis and response to treatment of cancer patients in recent years [5]. This study is aimed at exploring TME-associated biomarkers and identify their potential mechanism in the microenvironment of AML. We identified TME-associated differentially expressed genes (DEGs) carried out pathway enrichment analysis, protein-protein interaction (PPI) network, Cox regression analysis, and Kaplan-Meier survival analysis to select the most crucial genes. We further explored the potential mechanism of HCK in the AML microenvironment. We identified 624 TME-associated DEGs and found that HCK was the most promising biomarker associated with AML. HCK could regulate immune cell infiltration in the microenvironment of AML and may act as a potential biomarker for the treatment and prognosis of AML patients

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