MiR-181a-2-3p as a potential diagnostic and prognostic marker for myelodysplastic syndrome.

OBJECTIVE: Myelodysplastic syndrome (MDS) is a clonal bone marrow disorder with a high propensity to develop into acute myeloid leukemia (AML). Although abnormal microRNA expression has been implicated in MDS, the exact role of miR-181a-2-3p has not been entirely elucidated. Here, we investigated miR-181a-2-3p levels in bone marrow (BM), and described its utility as a potential indicator for MDS diagnosis and prognosis. METHODS: We evaluated miR-181a-2-3p expression in BM samples of 54 newly diagnosed MDS cases, 16 sAML patients and 32 healthy donors and then assessed its association with clinical characteristics and its potential value for MDS diagnosis and prognosis. RESULTS: Compared with healthy controls, miR-181a-2-3p levels were decreased in the total cohort of MDS patients. Additionally, in MDS patients with secondary AML (sAML), miR-181a-2-3p was over-expressed relative to levels in those without this form. The areas under the curve of receiver operating characteristic curves were 0.700 and 0.750 to distinguish MDS patients from controls and sAML from newly diagnosed MDS, respectively. Kaplan-Meier analysis showed a positive correlation between miR-181a-2-3p expression and overall survival (OS). Further, multivariate analysis indicated that miR-181a-2-3p was an independent prognostic index for MDS with respect to OS. CONCLUSION: Decreased miR-181a-2-3p expression in MDS patients may be considered as one of the underlying markers reflecting MDS progression and prognosis.

An immune-related gene prognostic index for acute myeloid leukemia associated with regulatory T cells infiltration.

Acute myeloid leukemia (AML) is a malignant clonal disease characterized by abnormal proliferation of immature myeloid cells and bone marrow failure. Regulatory T cells (Treg) play a suppressive role in the anti-tumor immune response in the tumor microenvironment. Screening biomarkers based on Treg immune-related genes may help to predict the prognosis and the efficacy of immunotherapy of AML.Gene expression profiles of AML (non-M3) were obtained from the TCGA and GEO databases. Gene module related to Treg was extracted using CIBERSORT and WGCNA algorithms. Univariate Cox regression and LASSO analyses were performed to identify hub genes and constructed the immune prognostic model. Molecular and immunological features associated with risk signature were explored, and TIDE was used to predict the efficacy of immunotherapy.A risk signature was constructed based on the five IRGs (IFI27L1, YIPF6, PARVB, TRIM32 and RHOBTB3). The risk signature could be served as an independent prognostic factor of AML. Patients in the high-risk group had a poorer OS than those in the low-risk group. In addition, patients in the high-risk group had higher TP53 mutation rate, higher infiltration of Treg, higher immune escape potential and less benefit from ICI therapy compared to low-risk group.Our study constructed a prognostic index based on five Treg-related biomarkers, which help to facilitate the differentiation of immunological and molecular characteristics of AML, predict patient prognosis and provide a reference for predicting benefits from ICI therapy.

Expression and clinical significance of RAG1 in myelodysplastic syndromes.

OBJECTIVE: To determine the expression level of RAG1 and its clinical significance in myelodysplastic syndromes (MDS). METHODS: To explore the candidate genes, the microarray datasets GSE19429, GSE58831, and GSE2779 were downloaded from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) in MDS were screened using RStudio, and overlapped DEGs were obtained with Venn Diagrams. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses, and protein-protein interaction network were performed. Quantitative real-time PCR (qRT-PCR) was employed to confirm the microarray results. RESULTS: This study identified 26 DEGs. Functional enrichment analyses indicated that these DEGs were significantly enriched in the immune response, and hematopoietic cell lineage. Eight core genes, for example, RAG1 and PAX5, were identified with a high degree of connectivity. The result of qRT-PCR showed that RAG1 was significantly down-regulated in MDS patients, which helped in distinguishing MDS patients from normal controls. The area under the curve of the receiver operator characteristic was 0.913 (P < 0.0001). MDS patients with low RAG1 expression level had a poor long-term survival (P = 0.031). What's more, the expression of RAG1 was significantly increased in the patients who received treatment. CONCLUSION: The results showed that the expression of RAG1 was down-regulated in MDS patients. Lower RAG1 expression was associated with adverse clinical outcomes. RAG1 may be a potential prognostic biomarker for MDS.