Dataset Information

Novel prognostic genes and subclasses of acute myeloid leukemia revealed by survival analysis of gene expression data.

ABSTRACT:

Background

Acute myeloid leukemia (AML) is biologically heterogeneous diseases with adverse prognosis. This study was conducted to find prognostic biomarkers that could effectively classify AML patients and provide guidance for treatment decision making.

Methods

Weighted gene co-expression network analysis was applied to detect co-expression modules and analyze their relationship with clinicopathologic characteristics using RNA sequencing data from The Cancer Genome Atlas database. The associations of gene expression with patients' mortality were investigated by a variety of statistical methods and validated in an independent dataset of 405 AML patients. A risk score formula was created based on a linear combination of five gene expression levels.

Results

The weighted gene co-expression network analysis detected 63 co-expression modules. The pink and darkred modules were negatively significantly correlated with overall survival of AML patients. High expression of FNDC3B, VSTM1 and CALR was associated with favourable overall survival, while high expression of PLA2G4A was associated with adverse overall survival. Hierarchical clustering analysis of FNDC3B, VSTM1, PLA2G4A, GOLGA3 and CALR uncovered four subgroups of AML patients. The cluster1 AML patients showed younger age, lower cytogenetics risk, higher frequency of NPM1 mutations and more favourable overall survival than cluster3 patients. The risk score was demonstrated to be an indicator of adverse prognosis in AML patients CONCLUSIONS: The FNDC3B, VSTM1, PLA2G4A, GOLGA3, CALR and risk score may serve as key prognostic biomarkers for the stratification and ultimately guide rational treatment of AML patients.

SUBMITTER: Lai Y

PROVIDER: S-EPMC7860023 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Publications

Novel prognostic genes and subclasses of acute myeloid leukemia revealed by survival analysis of gene expression data.

Lai Yanli Y OuYang Guifang G Sheng Lixia L Zhang Yanli Y Lai Binbin B Zhou Miao M

BMC medical genomics 20210203 1

<h4>Background</h4>Acute myeloid leukemia (AML) is biologically heterogeneous diseases with adverse prognosis. This study was conducted to find prognostic biomarkers that could effectively classify AML patients and provide guidance for treatment decision making.<h4>Methods</h4>Weighted gene co-expression network analysis was applied to detect co-expression modules and analyze their relationship with clinicopathologic characteristics using RNA sequencing data from The Cancer Genome Atlas database ...[more]

PMID: 33536020

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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.

Project description:BackgroundAs a severe hematological malignancy in adults, acute myeloid leukemia (AML) is characterized by high heterogeneity and complexity. Emerging evidence highlights the importance of the tumor immune microenvironment and lipid metabolism in cancer progression. In this study, we comprehensively evaluated the expression profiles of genes related to lipid metabolism and immune modifications to develop a prognostic risk signature for AML.MethodsFirst, we extracted the mRNA expression profiles of bone marrow samples from an AML cohort from The Cancer Genome Atlas database and employed Cox regression analysis to select prognostic hub genes associated with lipid metabolism and immunity. We then constructed a prognostic signature with hub genes significantly related to survival and validated the stability and robustness of the prognostic signature using three external datasets. Gene Set Enrichment Analysis was implemented to explore the underlying biological pathways related to the risk signature. Finally, the correlation between signature, immunity, and drug sensitivity was explored.ResultsEight genes were identified from the analysis and verified in the clinical samples, including APOBEC3C, MSMO1, ATP13A2, SMPDL3B, PLA2G4A, TNFSF15, IL2RA, and HGF, to develop a risk-scoring model that effectively stratified patients with AML into low- and high-risk groups, demonstrating significant differences in survival time. The risk signature was negatively related to immune cell infiltration. Samples with AML in the low-risk group, as defined by the risk signature, were more likely to be responsive to immunotherapy, whereas those at high risk responded better to specific targeted drugs.ConclusionsThis study reveals the significant role of lipid metabolism- and immune-related genes in prognosis and demonstrated the utility of these signature genes as reliable bioinformatic indicators for predicting survival in patients with AML. The risk-scoring model based on these prognostic signature genes holds promise as a valuable tool for individualized treatment decision-making, providing valuable insights for improving patient prognosis and treatment outcomes in AML.

Dataset Information

Novel prognostic genes and subclasses of acute myeloid leukemia revealed by survival analysis of gene expression data.

Background

Methods

Results

Publications

Novel prognostic genes and subclasses of acute myeloid leukemia revealed by survival analysis of gene expression data.

Similar Datasets

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