Tumor Microenvironmental Competitive Endogenous RNA Network and Immune Cells Act as Robust Prognostic Predictor of Acute Myeloid Leukemia

Abstract

Acute myeloid leukemia (AML) is malignant hematologic tumors with frequent recurrence and cause high mortality. Its fate is determined by abnormal intracellular competitive endogenous RNA (ceRNA) network and extracellular tumor microenvironment (TME). This study aims to build a ceRNA network related to AML TME to explore new prognostic and therapeutic targets. The RNA expression data of AML were obtained from The Cancer Genome Atlas (TCGA) database. First, we used the ESTIMATE algorithm to calculate the immune cells and stromal cells infiltration scores in the TME and found that all scores were highly correlated with AML’s prognostic characteristics. Subsequently, differentially expressed mRNAs and lncRNAs between high and low score groups were identified to construct a TME-related ceRNA network. Further, the Cox-lasso survival model was employed to screen out the hub prognostic ceRNA network composed of two mRNAs (EPB41L3, COL2A1), three miRNAs (hsa-mir-26a-5p, hsa-mir-148b-3p, hsa-mir-148a-3p), and two lncRNAs (CYP1B1-AS1, C9orf106), and construct nomograms. Finally, we used CIBERSORT algorithm and Kaplan-Meier survival analysis to identify the prognostic TME immune cells and found that naive B cells, M2-type macrophages, and helper follicular T cells were related to prognosis, and the hub ceRNAs were highly correlated with immune cell infiltration. This study provided a new perspective to elucidate how TME regulates AML process and put forward the new therapy strategies combining targeting tumor cells with disintegrating TME.

Identification and validation of a novel redox-related lncRNA prognostic signature in lung adenocarcinoma

“…It upregulates after exposure to hydrogen peroxide (oxidative stress), which is consistent with our proposal of its role as a redox-related lncRNA, and may become an indicator of stress responses [ 58 ]. CYP1B1-AS1 is emerging as a powerful prognostic indicator for acute myeloid leukemia (AML), and plays an important part in the intracellular biological process and extracellular microenvironment of AML cells [ 59 ]. Above all, the four lncRNAs in our signature showed potential impacts on multiple types of cancers.…”

Role of Circular RNAs in the Regulation of Immune Cells in Response to Cancer Therapies

“…The tumor microenvironment (TME) dynamically regulates a wide network of interactions between tumor, and stroma cells, in particular immune cells (Arneth, 2019). Although several reports show that long noncoding RNAs (lncRNAs) and circRNAs regulate the TME in solid tumors like prostate cancer, breast cancer and acute myeloid leukemia (Cheng et al, 2021;Jiang et al, 2021), there is no evidence of the interaction among lncRNA-circRNAs-mRNA for modulating the TME.…”

Deconvolution of Bulk Gene Expression Profiles with Single-Cell Transcriptomics to Develop a Cell Type Composition-Based Prognostic Model for Acute Myeloid Leukemia

“…Previous studies applying CIBERSORT to estimate the immune microenvironment for AML all used LM22, which contains the GESs of 22 immunocytes provided by the author as the reference matrix ( Newman et al, 2015 ; Xu et al, 2020 ; Cheng et al, 2021 ; Jia et al, 2021 ). However, the estimates of CTCs might be inaccurate in these studies because of the resemblance between normal immunocytes and malignant leukemic blasts, especially for the myeloid lineages—for example, both Xu et al (2020) and Cheng et al (2021) identified that higher relative proportions of M2 macrophage were associated with a poorer prognosis for AML. Additionally, Xu et al (2020) suggested the marker gene of M2 macrophage CD206, also presenting in immature dendritic cells (DCs) ( Wollenberg et al, 2002 ), as a novel prognostic predictor.…”