Prognostic significance of osteopontin in acute myeloid leukemia: A meta-analysis.
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ABSTRACT:
SUBMITTER: Chen YB
PROVIDER: S-EPMC5532631 | biostudies-other | 2017 Aug
REPOSITORIES: biostudies-other
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Project description:The 2-hydroxyglutarate (2-HG) has been reported to result from mutations of isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) genes and to function as an "oncometabolite." To evaluate the clinical significance of serum 2-HG levels in hematologic malignancies, acute myeloid leukemia (AML) in particular, we analyzed this metabolite in distinct types of human leukemia and lymphoma and established the range of serum 2-HG in appropriate normal control individuals by using gas chromatograph-time-of-flight mass spectrometry. Aberrant serum 2-HG pattern was detected in the multicenter group of AML, with 62 of 367 (17%) patients having 2-HG levels above the cutoff value (2.01, log2-transformed from 4.03 ?g/mL). IDH1/2 mutations occurred in 27 of 31 (87%) AML cases with very high 2-HG, but were observed only in 9 of 31 (29%) patients with moderately high 2-HG, suggesting other genetic or biochemical events may exist in causing 2-HG elevation. Indeed, glutamine-related metabolites exhibited a pattern in favor of 2-HG synthesis in the high 2-HG group. In AML patients with cytogenetically normal AML (n = 234), high 2-HG represented a negative prognostic factor in both overall survival and event-free survival. Univariate and multivariate analyses confirmed high serum 2-HG as a strong prognostic predictor independent of other clinical and molecular features. We also demonstrated distinct gene-expression/DNA methylation profiles in AML blasts with high 2-HG compared with those with normal ones, supporting a role that 2-HG plays in leukemogenesis.
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Project description:BackgroundDespite deeper understanding of the genetic landscape of acute myeloid leukemia (AML), the improvement of survival is still a great challenge. STK10 is overexpressed in several cancers with functions varying according to cancer types. But the functions of STK10 in AML has never been reported.MethodsWe analyzed the expression, prognosis and potential functions of STK10 utilizing public web servers. Metascape and the String database were used for functional and protein-protein interaction analyses.ResultsWe found STK10 was enriched in blood & immune cells and overexpressed in AML. High STK10 expression was associated with poor overall survival, which was also identified in the subgroups of patients ≤ 60 years old and patients with non-high-risk cytogenetics. We demonstrated genes associated with STK10 were enriched in blood, spleen and bone marrow, influencing the immune function and biological process of AML. ITGB2 and ITGAM might directly interact with STK10 and were associated with poor prognosis. Besides, STK10 was associated with the infiltration of immune cells and immune checkpoints, like HLA-E, CD274 and GAL-9.ConclusionsThe present study was the original description of STK10 in AML and set the stage for developing STK10 as a new prognostic marker or therapeutic target for AML.
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Project description:Interferon regulatory factor 8 (IRF8) is a transcription factor that plays a critical role in normal hematopoiesis, such that disruption of IRF8 activity promotes leukemogenesis. We and others have identified aberrant expression of IRF8 transcripts, including novel splice variants, in acute myeloid leukemia (AML), but studies have not investigated the prognostic significance of these transcripts. Therefore, we developed and optimized quantitative expression assays for both, the wild type, or the reference sequence (WT-IRF8) and novel splice variants (SV-IRF8). These assays were used to quantify IRF8 transcript levels in 194 adult patients with AML, and multivariate analyses investigated the prognostic significance of these expression levels. After adjusting for known prognostic factors, expression levels of WT- or SV-IRF8 transcripts were not significantly associated with complete responses or overall survival. However, increased expression of WT-IRF8 was associated with decreased relapse-free survival (RFS) in both univariate (P?=?0.010) and multivariate (P?=?0.019) analyses. Similarly, increased expression of SV-IRF8 was associated with a decreased RFS (univariate, P?=?0.026 and multivariate, P?=?0.021). These studies show for the first time that WT-IRF8 and SV-IRF8 are independent adverse prognostic factors for patients with AML. Additional studies are planned to examine the prognostic significance of IRF8 transcripts in other populations of AML patients.
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Project description:BackgroundStudy results on the prognostic value of CD11b for acute myeloid leukemia (AML) patients are inconsistent. An up-to-date meta-analysis was conducted to assess the prognostic value of CD11b expression level for AML patients.MethodsElectronic databases including PubMed, Embase, Cochrane Library, Web of Science and Chinese BioMedical Literature Database (CBM) were searched to identify studies that investigated the association between CD11b expression level and prognosis of AML patients. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) for overall survival (OS) and disease-free survival (DFS) and pooled odds ratio (OR) with 95% CI for complete remission rate (CRR) were calculated using Revman 5.3 and Stata 11.0.Results13 total studies with 2619 patients were included in this meta-analysis. Results of the meta-analysis showed that CD11b positivity was associated with lower CRR (OR = 0.44; 95% CI, 0.25-0.79; p = 0.006) and shorter OS (HR = 0.66; 95% CI, 0.55-0.80; p < 0.0001), but did not affect DFS (HR = 0.67; 95% CI, 0.31-1.48; p = 0.32). Subgroup analysis by ethnicity, cut-off value for CD11b positivity, treatment, subtype and sample preparation method showed no significant interaction between these factors with the prognostic value of CD11b expression level for AML patients. Sensitivity analysis yielded consistent results with the main meta-analysis.ConclusionCD11b positivity could predict a poor prognosis for AML patients. Thus, CD11b expression level might be considered a prognostic biomarker for AML patients.
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