High expression of miR-107 and miR-17 predicts poor prognosis and guides treatment selection in acute myeloid leukemia

Abstract

Background:The prognostic significance of miR-107 and miR-17 in patients with acute myeloid leukemia (AML) remains unclear.Methods: A total of 173 patients with de novo AML from the Cancer Genome Atlas database were enrolled in this study and further divided into a chemotherapy group (98 cases) and an allogeneic hematopoietic stem cell transplantation (allo-HSCT) group (75 cases) according to their therapy regimen.Results: In the chemotherapy cohort, high miR-107 or miR-17 expression was associated with poorer overall survival (OS) and event-free survival (EFS). On the other hand, there were no significant differences in OS and EFS between the high-and low-expression subgroups in the allo-HSCT group. Next, we stratified the total number of patients with AML into high-and low-expression groups according to the median expression levels of miR-107 or miR-17. In the high miR-107 or miR-17 expression group, patients treated with allo-HSCT had longer OS than those treated with chemotherapy. In the low miR-107 or miR-17 expression group, no significant differences in OS and EFS were observed between the two therapy subgroups. When patients were further clustered into three groups (both low miR-107 and low miR-17, either high miR-107 or high miR-17, and both high miR-107 and high miR-17), patients with both high miR-107 and high miR-17 expression had the worst OS and EFS of the entire group and of the chemotherapy group. On the other hand, there were no significant differences in OS and EFS among the three subgroups in the allo-HSCT group. Cox regression confirmed the concurrence of high expression of miR-107 and miR-17 might act as an independent prognostic factor for EFS and OS in the entire group and the chemotherapy group. Bioinformatics analysis showed differentially expressed genes (DEGs) associated with miR-107 and miR-17 expression were mainly enriched in multiple metabolic processes. Conclusions:The combination of miR-107 and miR-17 provides prognostic significance for patients with AML and should be considered in the clinical selection of the optimal treatment regimen when deciding between chemotherapy and allo-HSCT.

miRNAs as prognostic predictors in acute myeloid leukemia

“…In the present issue, Liu et al ( 6 ) reported that high expression of miR-107 and miR-17 is associated with worse clinical outcomes in patients with AML who received chemotherapy, which was not observed in the group of patients who received allo-HSCT. When analyzed together, patients with high expression of both miR-107 and miR-17 had the worst clinical outcomes (entire cohort and chemotherapy group).…”

“…When analyzed together, patients with high expression of both miR-107 and miR-17 had the worst clinical outcomes (entire cohort and chemotherapy group). From the biological point of view, analysis of differentially expressed genes revealed a potential association of these miRNAs with the dysregulation of multiple metabolic processes ( 6 ).…”

“…Despite the study by Liu et al ( 6 ) being a pioneer in the study of miR-107 and miR-17 in AML, the role of miRNAs has been widely explored in the field of oncology, and their contribution has been reported for different types of cancers. Among the solid tumors that show increased miR-107 expression gastric cancer, breast cancer, penile cancer, hepatocellular carcinoma, and colorectal cancer stand out ( 7 - 11 ).…”

Effective Prognostic Model for Therapy Response Prediction in Acute Myeloid Leukemia Patients

“…For example, in the study of Xu et al, tight associations between the high expression of TSC22D3 domain family genes playing an essential role in tumor progression with poor overall and event-free survival and drug resistance to BCL2 inhibitors in adult AML patients, especially in the chemotherapy group, have been reported [ 47 ]. The study of Liu et al demonstrated that high miR-107 or miR-17 expression levels were associated with poorer overall survival and event-free survival in the chemotherapy cohort of patients with de novo AML [ 48 ]. A special place is occupied by immunity-associated biomarkers, such as immune-related long noncoding RNAs [ 49 ] and immune microenvironment genes [ 50 ], which are closely related to resistance to immunotherapy and poor prognosis for AML patients.…”

MicroRNAs Associated with a Bad Prognosis in Acute Myeloid Leukemia and Their Impact on Macrophage Polarization

“…Thus, in MLL, where the abovementioned miRNAs are overexpressed, targeting both miR-17-5p and miR-19a-3p by antagomiRs reduces the ability of MLL cells to form colonies compared to non-MLL AML controls [58]. Several other studies suggested that the miR-17 cluster is associated with a poor prognosis [33,59] through several mechanisms, including the promotion of leukemic blast proliferation [60]. With regard to macrophage polarization, miR-17 and miR-20a promote an M1 phenotype by inhibiting signal-regulatory protein a (SIRPa) [60].…”