ABSTRACT
Background: Cytogenetics at diagnosis is the most important prognostic factor for adult acute myeloid leukemia (AML), but nearly 50% of AML patients who exhibit cytogenetically normal AML (CN-AML) do not undergo effective risk stratification. Therefore, the development of potential biomarkers to further define risk stratification for CN-AML patients is worth exploring. Methods: Transcriptome data from 163 cases in the GSE12417-GPL96 dataset and 104 CN-AML patient cases in the GSE71014-GPL10558 dataset were downloaded from the Gene Expression Omnibus database for overall survival (OS) analysis and validation. Results: The combination of Wilms tumor 1 (WT1) and cluster of diffraction 58 (CD58) can predict the prognosis of CN-AML patients. High expression of WT1 and low expression of CD58 were associated with poor OS in CN-AML. Notably, when WT1 and CD58 were used to concurrently predict OS, CN-AML patients were divided into three groups: low risk, WT1lowCD58high; intermediate risk, WT1highCD58high or WT1lowCD58low; and high risk, WT1highCD58low. Compared with low-risk patients, intermediate- and high-risk patients had shorter survival time and worse OS. Furthermore, a nomogram model constructed with WT1 and CD58 may personalize and reveal the 1-, 2-, 3-, 4-, and 5-year OS rate of CN-AML patients. Both time-dependent receiver operating characteristics and calibration curves suggested that the nomogram model demonstrated good performance. Conclusion: Higher expression of WT1 with lower CD58 expression may be a potential biomarker for risk stratification of CN-AML patients. Moreover, a nomogram model constructed with WT1 and CD58 may personalize and reveal the 1-, 2-, 3-, 4-, and 5-year OS rates of CN-AML patients.
Subject(s)
Biomarkers, Tumor , CD58 Antigens/genetics , Gene Expression Regulation, Leukemic , Leukemia, Myeloid, Acute/genetics , WT1 Proteins/genetics , CD58 Antigens/metabolism , Computational Biology , Cytogenetic Analysis , Databases, Genetic , Gene Expression Profiling , Humans , Leukemia, Myeloid, Acute/diagnosis , Leukemia, Myeloid, Acute/metabolism , Prognosis , Proportional Hazards Models , Transcriptome , WT1 Proteins/metabolism , WorkflowABSTRACT
OBJECTIVES: Previous study (Br. J. Haematol. 2017; 176:498) reported that CD56 positive is associated with poor prognosis of patients with intermediate-risk acute myeloid leukemia (IR-AML). However, our data were inconsistent with the finding. Thus, in this study, we provided the different results to discuss. METHODS: A total of 262 bone marrow transcriptomic data of IR-AML in the GSE12417-GPL96 and GSE71014-GPL-10558 from the Gene Expression Omnibus database (GEO) database, and 92 IR-AML patients from the cancer genome atlas (TCGA) database were obtained for prognostic analysis and validation. RESULTS: Compared with low CD56 expression, IR-AML patients with high CD56 expression had a longer overall survival (OS) time and restricted mean survival time (RMST) and favorable OS rate in the GSE12417-GPL96 dataset. These results were confirmed in both GSE71014-GPL-10558 and TCGA datasets. Importantly, the inconsistency between our findings and the previous finding may be due to the following reasons: different detection methods, age stratification, countries, treatment options etc. CONCLUSIONS: The prognostic value of CD56 expression in IR-AML may need to be comprehensively evaluated based on different detection methods, age stratification, countries, treatment options, and other factors. If confirmed, CD56 may be a biomarker for further risk stratification for IR-AML patients.
Subject(s)
Biomarkers, Tumor , CD56 Antigen/genetics , Gene Expression , Leukemia, Myeloid, Acute/etiology , Leukemia, Myeloid, Acute/mortality , Adolescent , Adult , Aged , Aged, 80 and over , Bone Marrow Cells/metabolism , Bone Marrow Examination , CD56 Antigen/metabolism , Combined Modality Therapy , Female , Gene Expression Profiling , Humans , Immunophenotyping , Leukemia, Myeloid, Acute/diagnosis , Leukemia, Myeloid, Acute/metabolism , Male , Middle Aged , Prognosis , Young AdultABSTRACT
Immunotherapy with immune checkpoint inhibitors (ICIs) for solid tumors had significantly improved overall survival. This type of therapy is still not available for acute myeloid leukemia (AML). One major issue is the lack of knowledge for the expression patterns of immune checkpoints (IC) in AML. In this study, we first explored the prognostic value of ICs for AML patients by analyzing RNA-seq and mutation data from 176 AML patients from the Cancer Genome Atlas (TCGA) database. We further validated the results of the database analysis by analyzing bone marrow (BM) samples from 62 patients with de novo AML. Both TCGA data and validation results indicated that high expression of PD-1, PD-L1, and PD-L2 was associated with poor overall survival (OS) in AML patients. In addition, increased co-expression of PD-1/CTLA-4 or PD-L2/CTLA-4 correlated with poor OS in AML patients (3-year OS: TGCA data 30% vs 0% and 20% vs 0%, validation group 57% vs 31% and 57% vs 33%, respectively) (P < 0.05). Moreover, co-expression of PD-1/PD-L1, PD-1/PD-L1/PD-L2, and PD-1/LAG-3 was found to correlate with poor OS in AML patients with FLT3mut, RUNX1mut, and TET2mut, respectively. In conclusion, high expression of ICs in the BM leukemia cells of AML patients correlated with poor outcome. The co-expression patterns of PD-1/CTLA-4, PD-L2/CTLA-4, PD-1/PD-L1, PD-1/PD-L1/PD-L2, and PD-1/LAG-3 might be potential immune biomarkers for designing novel AML therapy.
