The M2 macrophage marker CD206: a novel prognostic indicator for acute myeloid leukemia.
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ABSTRACT:
SUBMITTER: Xu ZJ
PROVIDER: S-EPMC6959428 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundIt has been demonstrated that aberrant expression of serum microRNAs is potential markers for the prognostic prediction of acute myeloid leukemia (AML). However, the clinical significance of serum miR-22 remained uncovered. In this study, we aimed to explore the potential prognostic value of serum miR-22 for AML.MethodsBlood samples were collected from 124 patients with AML and 60 healthy individuals. Serum miR-22 level was detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and its potential clinical value was investigated.ResultsOur results showed that serum miR-22 expression was significantly downregulated in AML subjects compared to healthy controls. Serum miR-22 levels were lowest in AML patients with M4/M5 subtypes, and low serum miR-22 expression occurred more frequently in AML patients with higher white blood cell counts or poor cytogenetic risk. Receiver operating characteristic (ROC) analysis revealed that serum miR-22 well differentiated AML cases from healthy controls. In addition, serum miR-22 downregulation was closely associated with worse clinical features and shorter survival. Low serum miR-22 expression was confirmed to be an independent predictor for overall survival and relapse-free survival in AML patients. Moreover, the expression level of serum miR-22 was dramatically increased following treatment. In addition, serum miR-22 levels were significantly higher in AML patients achieving complete remission (CR) than those without CR.ConclusionCollectively, serum miR-22 might serve as a novel and promising prognostic biomarker for AML.
| S-EPMC7521259 | biostudies-literature
Project description:BackgroundThe overexpression of ALOX5AP has been observed in many types of cancer and has been identified as an oncogene. However, its role in acute myeloid leukemia (AML) has not been extensively studied. This study aimed to identify the expression and methylation patterns of ALOX5AP in bone marrow (BM) samples of AML patients, and further explore its clinical significance.MethodsEighty-two de novo AML patients and 20 healthy donors were included in the study. Meanwhile, seven public datasets from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) were included to confirm the alteration of ALOX5AP. Receiver operating characteristic (ROC) curve analysis was applied to determine the discriminative capacity of ALOX5AP expression to discriminate AML. The prognostic value of ALOX5AP was identified by the Kaplan-Meier method and log-rank test. It was further validated in four independent cohorts (n = 1186). Significantly different genes associated with ALOX5AP expression were subsequently compared by LinkedOmics, and Metascape database.ResultsThe level of ALOX5AP expression was significantly increased in bone marrow cells of AML patients compared with healthy donors (P < 0.05). ROC curve analysis suggested that ALOX5AP expression might be a potential biomarker to discriminate AML from controls. ALOX5AP overexpression was associated with decreased overall survival (OS) in AML according to the TCGA data (P = 0.006), which was validated by other four independent cohorts. DNA methylation levels of ALOX5AP were significantly lower in AML patients compared to normal samples (P < 0.05), as confirmed in the Diseasemeth database and the independent cohort GSE63409. ALOX5AP level was positively associated with genes with proleukemic effects such as PAX2, HOX family, SOX11, H19, and microRNAs that act as oncogenes in leukemia, such as miR125b, miR-93, miR-494, miR-193b, while anti-leukemia-related genes and tumor suppressor microRNAs such as miR-582, miR-9 family and miR-205 were negatively correlated.ConclusionALOX5AP overexpression, associated with its hypomethylation, predicts poorer prognosis in AML.
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Project description:BackgroundLong noncoding RNAs (lncRNA) play a role in leukemogenesis, maintenance, development, and therapeutic resistance of AML. While few studies have focused on the prognostic significance of LINC00649 in AML, which we aim to investigate in this present study.MethodsWe compared the expression level of LINC00649 between AML patients and healthy controls. The Kaplan-Meier curves of AML patients expressing high versus low level of LINC00649 was performed. The LINC00649 correlated genes/miRNAs/lncRNAs and methylation CpG sites were screened by Pearson correlation analysis with R (version 3.6.0), using TCGA-LAML database. The LINC00649 associated ceRNA network was established using lncBase 2.0 and miRWalk 2.0 online tools, combining results from correlation analysis. Finally, a prediction model was constructed using LASSO-Cox regression.ResultsLINC00649 was underexpressed in bone marrow of AML group than that in healthy control group. The patients of LINC00649-low group have significantly inferior PFS and OS. A total of 154 mRNAs, 31 miRNAs, 28 lncRNAs and 1590 methylated CpG sites were identified to be significantly correlated with LINC00649. Furthermore, the network of ceRNA was established with 6 miRNAs and 122 mRNAs. The Lasso-Cox model fitted OS/PFS to novel prediction models, which integrated clinical factors, ELN risk stratification, mRNA/miRNA expression and methylation profiles. The analysis of time-dependent ROC for our model showed a superior AUC (AUC = 0.916 at 1 year, AUC = 0.916 at 3 years, and AUC = 0.891 at 5 years).ConclusionsLow expression of LINC00649 is a potential unfavorable prognostic marker for AML patients, which requires the further validation. The analysis by LASSO-COX regression identified a novel comprehensive model with a superior diagnostic utility, which integrated clinical and genetic variables.
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Project description:Rho-related BTB domain (RhoBTB) proteins belong to Rho guanosine triphosphatases (GTPases). Their putative role implicated in carcinogenesis has been supported by accumulating evidence. However, their expression pattern and potential role in acute myeloid leukemia (AML) remain unclear. We profiled RHOBTB mRNA expression via the Gene Expression Profiling Interactive Analysis 2 (GEPIA2) database. Survival analysis was conducted with GEPIA2 and UALCAN. Univariate and multivariate Cox regression analyses were performed to validate RHOBTB genes as independent prognostic indicators in the LAML cohort from The Cancer Genome Atlas (TCGA). Data regarding expression in different subtypes and relationships with common disease-related genes were retrieved from UALCAN. Co-expressed genes were screened out and subsequently subjected to functional enrichment analysis. We observed aberrant transcription levels of RHOBTB genes in AML patients. RHOBTB2 was identified as a prognostic candidate for overall survival (OS), independent of prognosis-related clinical factors and genetic abnormalities. Moreover, RHOBTB2 expression was increased in non-acute promyelocytic leukemia (APL) subtypes, patients without FLT3 mutation and PML/RAR fusion, and imparted a positive correlation with the expression of FLT3, FHL1, and RUNXs. Co-expressed genes of RHOBTB2 were enriched in functional pathways in AML. Our findings suggest that RHOBTB2 might be a novel biomarker and independent prognostic indicator in AML and provide insights into the leukemogenesis and molecular network of AML.
| S-EPMC8221349 | biostudies-literature
Project description:Acute myeloid leukemia (AML) is a biologically complex and molecularly and clinically heterogeneous disease, and its incidence increases with age. Cytogenetics and mutation testing remain important prognostic tools for treatment after induction therapy. The post-induction treatment is dependent on risk stratification. Despite rapid advances in determination of gene mutations involved in the pathophysiology and biology of AML, and the rapid development of new drugs, treatment improvements changed slowly over the past 30 years, with the majority of patients eventually experiencing relapse and dying of their disease. Allogenic hematopoietic stem cell transplantation remains the best chance of cure for patients with intermediate- or high-risk disease. This review gives an overview about advances in prognostic markers and novel treatment options for AML, focusing on new prognostic and probably therapeutic mutations, and novel drug therapies such as tyrosine kinase inhibitors.
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Project description:EPAS1 plays an important role in the development and progression of multiple tumor types by interacting with a series of other molecules. However, the prognostic and diagnostic values of EPAS1 in acute myeloid leukemia (AML) remain unknown. Here, we systematically explored and clarified the potential functions of EPAS1 in AML using data from Xena Browser and TCGA database. The expression of EPAS1 was significantly lower in AML patients than that in healthy people. The GO, KEGG, GSEA, and GSVA were performed to explore the potential functions and signaling pathways. The survival analysis was conducted using Cox regression analysis and the Kaplan-Meier method. Immune cell infiltration was evaluated via single-sample GSEA (ssGSEA). The results of enrichment analyses suggested that low-EPAS1 expression was related to the initiation, development, and prognosis of AML. The immune microenvironment landscape in AML was described by ssGSEA. ROC analysis of EPAS1 showed high discrimination ability between AML patients and healthy people. Kaplan-Meier method indicated that low-EPAS1 expression correlated significantly with a poor overall survival. Multivariate Cox regression analysis revealed that both age and EPAS1 expression were independent prognostic factors in AML patients. Furthermore, the nomogram based on these two variables performed well in discrimination and calibration. In summary, our study may provide new insights into the molecular mechanisms underlying AML and demonstrate the diagnostic and prognostic value of EPAS1 in AML for the first time.
| S-EPMC10137199 | biostudies-literature
Project description:It has been recently shown that DNA methyl transferase overexpression is correlated with unfavourable prognosis in human malignancies while methylation deregulation remains a hallmark that defines acute myeloid leukemia (AML). The oncogenic transcription factor EVI1 is involved in methylation deregulation and its overexpression plays a major role for predicting an adverse outcome. Moreover, the identification of DNMT3A mutations in AML patients has recently been described as a poor prognostic indicator. In order to clarify relationship between these key actors in methylation mechanisms and their potential impact on patient outcomes, we analysed 195 de novo AML patients for the expression of DNMT3A, 3B (and its non-catalytic variant 3B(NC)) and their correlations with the outcome and the expression of other common prognostic genetic biomarkers (EVI1, NPM1, FLT3ITD/TKD and MLL) in adult AML. The overexpression of DNMT3B/3B(NC) is (i) significantly correlated with a shorter overall survival, and (ii) inversely significantly correlated with event-free survival and DNMT3A expression level. Moreover, multivariate analysis showed that a high expression level of DNMT3B/3B(NC) is statistically a significant independent poor prognostic indicator. This study represents the first report showing that the overexpression of DNMT3B/3B(NC) is an independent predictor of poor survival in AML. Its quantification should be implemented to the genetic profile used to stratify patients for therapeutical strategies and should be useful to identify patients who may benefit from therapy based on demethylating agents.
| S-EPMC3519733 | biostudies-literature
Project description:BackgroundAcute myeloid leukemia (AML) is a clonal malignant disease with poor prognosis and a low overall survival rate. Although many studies on the treatment and detection of AML have been conducted, the molecular mechanism of AML development and progression has not been fully elucidated. The present study was designed to pursuit the molecular mechanism of AML using a comprehensive bioinformatics analysis, and build an applicable model to predict the survival probability of AML patients in clinical use.MethodsTo simplify the complicated regulatory networks, we performed the gene co-expression and PPI network based on WGCNA and STRING database using modularization design. Two machine learning methods, A least absolute shrinkage and selector operation (LASSO) algorithm and support vector machine-recursive feature elimination (SVM-RFE), were used to filter the common hub genes by five-fold cross-validation. The candidate hub genes were used to build the predictive model of AML by the cox-proportional hazards analysis, and validated in The Cancer Genome Atlas (TCGA) cohort and ohsu cohort, which were reliable in the experimental verification by qRT-PCR and western blotting in mRNA and protein levels.ResultsThree hub genes, FLT3, CD177 and TTPAL were used to build a clinically applicable model to predict the survival probability of AML patients and divided them into high and low groups. To compare the survival ability of the model with the classical clinical features, we generated the nomogram. The model displayed the most risk points contrast to other clinical characteristics, which was compatible with the data of cox multivariate regression.ConclusionThis study reveal the novel molecular mechanism of AML, and construct a clinical model significantly related to AML patient prognosis. We showed the integrated roles of critical pathways, hub genes associated, which provide potential targets and new research ideas for the treatment and early detection of AML.
| S-EPMC7655922 | biostudies-literature
Project description:Dysregulation of cytokines and growth factors is a general feature of tumor microenvironment, and unraveling the expression spectrum of cytokine and growth factor in niche is of utmost importance. Here, we evaluated cytokine profiling of bone marrow serum samples in AML patients and healthy controls. Protein expression profiling of serum from nine AML patients and five healthy controls was obtained using a biotinylated antibody chip. A total of 507 cytokines and growth factors were analyzed. Compared with healthy people, AML patients expressed 31 signature proteins, among which, 27 were significantly higher expressed and 4 proteins were lower. When patients were divided into favorable and poor prognosis, 12 signature proteins were significantly differentially expressed between these two groups. Furthermore, in order to identify the accuracy of cytokine expression profiles, we verified and analyzed the expression of THBS1 (Thrombospondin 1) in 116 patients and 9 healthy people. We found that THBS1 was lowly expressed in AML patients, which might be induced by promoter methylation, and patients with low THBS1 possessed shorter survivor time. Our data indicated that we successfully unveil differentially expressed proteins in AML patients using a biotinylated antibody chip; among them, THBS1 may be a potential therapeutic target for AML patients' treatment.
| S-EPMC7020255 | biostudies-literature
Project description:Acute myeloid leukemia (AML) is a common hematological malignancy in adults. AML patients exhibit clinical heterogeneity with complications of molecular basis. The leukemogenesis of AML involves immune escape, and the immunosuppression status of the patient might have great impact on AML treatment outcome. In this study, we established an immune prognostic model of AML using bioinformatics tools. With the data in the TCGA and GTEx datasets, we analyzed differentially expressed genes (DEGs) in non-M3 AML and identified 420 immune-related DEGs. Among which, 49 genes' expression was found to be related to AML prognosis based on univariate Cox regression analysis. Next, we established a prognostic model with these 49 genes in AML by LASSO regression and multivariate Cox regression analyses. In our model, the expressions of 5 immune genes, MIF, DEF6, OSM, MPO, AVPR1B, were used to stratify non-M3 AML patients' treatment outcome. A patient's risk score could be calculated as Risk Score=0.40081 × MIF (MIF expression) - 0.15201 × MPO + 0.78073 × DEF6 - 0.45192 × AVPR1B + 0.25912 × OSM. The area under the curve of the risk score signature was 0.8, 0.8, and 0.96 at 1 year, 3 years, and 5 years, respectively. The prognostic model was then validated internally by TCGA data and externally by GEO data. At last, the result of single-sample gene-set enrichment analysis demonstrated that compared with healthy samples, the abundance of non-turmeric immune cells was significantly repressed in AML. To summarize, we presented an immune-related 5-gene signature prognostic model in AML.
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