Abstract
Background: Metabolic reprogramming is the core characteristic of tumors during the development of tumors, and cancer cells can rely on metabolic changes to support their rapid growth. Nevertheless, an overall analysis of metabolic markers in acute myeloid leukemia (AML) is absent and urgently needed.Methods: Within this work, genetic expression, mutation data and clinical data of AML were queried from Genotype-Tissue Expression (GTEx) database, The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) database. The tumor samples of TCGA were randomly divided into a training group (64 samples) and an internal validation group (64 samples) at one time, and the tumor samples of GEO served as two external validation groups (99 samples, 374 samples). According to the expression levels of survival-associated metabolic genes, we divided all TCGA tumor samples into high, medium and low metabolism groups, and evaluated the immune cell activity in the tumor microenvironment of the three metabolism groups by single-sample gene set enrichment analysis (ssGSEA) algorithm. Finally, we examined the mutations and prognostic effects of each model gene.Results: Four metabolism-related genes were screened and applied to construct a prognostic model for AML, giving excellent results. As for the area under the curve (AUC) value of receiver operating characteristic (ROC) curve, the training group was up to 0.902 (1-year), 0.81 (3-year), and 0.877 (5-year); and the internal and external validation groups also met the expected standards, showing high potency in predicting patient outcome. Univariate and multivariate prognostic analyses indicated that the riskScore obtained from our prognostic model was an independent prognostic factor. ssGSEA analysis revealed the high metabolism group had higher immune activity. Single and multiple gene survival analysis validated that each model gene had significant effects on the overall survival of AML patients.Conclusions: In our study, a high-efficiency prognostic prediction model was built and validated for AML patients. The results showed that metabolism-related genes could become potential prognostic biomarkers for AML.
Highlights
acute myeloid leukemia (AML) is a malignant disease of myeloid hematopoietic stem/progenitor cells, which is mainly characterized by primitive and immature myeloid cell dysplasia in the bone marrow and peripheral blood
The metabolic prognostic model constructed by the training group showed excellent predictive performance after the double validation and the model gene survival analysis. These results provide a basic direction for further exploration of the molecular mechanism and diagnostic markers of AML
After univariate COX analysis (P < 0.01) for the training group (Supplementary File 7), we put the 12 survival-related metabolic genes obtained into the least absolute shrinkage and selection operator (LASSO) algorithm (Figures 2A,B)
Summary
AML is a malignant disease of myeloid hematopoietic stem/progenitor cells, which is mainly characterized by primitive and immature myeloid cell dysplasia in the bone marrow and peripheral blood. Its clinical manifestations are anemia, hemorrhage, infection and fever, organ infiltration and metabolic abnormality, etc. The condition is urgent and severe, and the prognosis is poor, which may endanger life if not treated in time [1]. Chemotherapy, targeted drugs and hematopoietic stem cell transplantation are still the main approaches for AML treatment. Even the most ideal treatment methods such as intensive chemotherapy and allogeneic hematopoietic stem cell (HSC) transplantation, the cure rate is relatively low [2]. It is urgent to explore new and accurate biomarkers to evaluate the diagnosis and prognosis of AML patients. An overall analysis of metabolic markers in acute myeloid leukemia (AML) is absent and urgently needed
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