Dataset Information

The Solute Carrier Family 2 Genes Are Potential Prognostic Biomarkers in Acute Myeloid Leukemia.

ABSTRACT: AIMS:The solute carrier family 2 (SLC2) genes are comprised of 14 members which are essential for the maintenance of glucose uptake and survival of tumour cells. This study was performed to investigate the associations of SLC2 family gene expression with mortality in acute myeloid leukemia (AML). METHODS:Clinical features and SLC2 family gene expression data were obtained from The Cancer Genome Atlas and Gene Expression Omnibus database. The associations between SLC2 family gene expression and clinicopathologic features were analyzed using linear regression model. Kaplan-Meier survival, univariate, multivariate survival analyses and validation analysis were performed to analyze the associations between SLC2 family gene expression and patients' overall survival. RESULTS:Patient mortality was positively associated with age and cytogenetic risk in AML patients. Kaplan-Meier survival analysis suggested that patients with high SLC2A5 and SLC2A10 expression showed poorer survival than those with low SLC2A5 and SLC2A10 expression. In contrast, patients with high SLC2A13 expression exhibited better prognosis than those with low SLC2A13 expression (P < 0.05 for all cases, log rank test). Multivariate survival analysis and validation analysis confirmed that high expression of SLC2A5 and SLC2A10 and low expression of SLC2A13 were associated with increased mortality (P = 0.00, Odd ratio [OR]:4.05, 95% Confidence Interval [CI]: 1.73-10.22; P = 0.00, OR: 3.66, 95% CI: 1.54-9.25; and P = 0.01, OR: 0.26, 95% CI: 0.09-0.68, respectively). CONCLUSION:SLC family gene expression, such as SLC2A5, SLC2A10 and SLC2A13, was significantly associated with prognosis of AML patients, their expression levels might become useful prognostic biomarkers in AML.

SUBMITTER: Lai B

PROVIDER: S-EPMC7099669 | biostudies-literature | 2020 Jan-Dec

REPOSITORIES: biostudies-literature

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The Solute Carrier Family 2 Genes Are Potential Prognostic Biomarkers in Acute Myeloid Leukemia.

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

Technology in cancer research & treatment 20200101

<h4>Aims</h4>The solute carrier family 2 (SLC2) genes are comprised of 14 members which are essential for the maintenance of glucose uptake and survival of tumour cells. This study was performed to investigate the associations of SLC2 family gene expression with mortality in acute myeloid leukemia (AML).<h4>Methods</h4>Clinical features and SLC2 family gene expression data were obtained from The Cancer Genome Atlas and Gene Expression Omnibus database. The associations between SLC2 family gene e ...[more]

PMID: 31918632

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Project description:The dysregulation of some solute carrier (SLC) proteins has been linked to a variety of diseases, including diabetes and chronic kidney disease. However, SLC-related genes (SLCs) has not been extensively studied in acute myocardial infarction (AMI). The GSE66360 and GSE60993 datasets, and SLCs geneset were enrolled in this study. Differentially expressed SLCs (DE-SLCs) were screened by overlapping DEGs between the AMI and control groups and SLCs. Next, functional enrichment analysis was carried out to research the function of DE-SLCs. Consistent clustering of samples from the GSE66360 dataset was accomplished based on DE-SLCs selected. Next, the gene set enrichment analysis (GSEA) was performed on the DEGs-cluster (cluster 1 vs cluster 2). Three machine learning models were performed to obtain key genes. Subsequently, biomarkers were obtained through receiver operating characteristic (ROC) curves and expression analysis. Then, the immune infiltration analysis was performed. Afterwards, single-gene GSEA was carried out, and the biomarker-drug network was established. Finally, quantitative real-time fluorescence PCR (qRT-PCR) was performed to verify the expression levels of biomarkers. In this study, 13 DE-SLCs were filtered by overlapping 366 SLCs and 448 DEGs. The functional enrichment results indicated that the genes were implicated with amino acid transport and TNF signaling pathway. After the consistency clustering analysis, the samples were classified into cluster 1 and cluster 2 subtypes. The functional enrichment results showed that DEGs-cluster were implicated with chemokine signaling pathway and so on. Further, SLC11A1 and SLC2A3 were identified as SLC-related biomarkers, which had the strongest negative relationship with resting memory CD4 T cells and the strongest positive association with activated mast cells. In addition, the single-gene GSEA results showed that cytosolic ribosome was enriched by the biomarkers. Five drugs targeting SLC2A3 were predicted as well. Lastly, the experimental results showed that the biomarkers expression trends were consistent with public database. In this study, 2 SLC-related biomarkers (SLC11A1 and SLC2A3) were screened and drug predictions were carried out to explore the prediction and treatment of AMI.

Project description:IntroductionAcute myeloid leukemia (AML) is an aggressive blood cancer with high heterogeneity and poor prognosis. Although the metabolic reprogramming of nicotinamide adenine dinucleotide (NAD) has been reported to play a pivotal role in the pathogenesis of acute myeloid leukemia (AML), the prognostic value of NAD metabolism and its correlation with the immune microenvironment in AML remains unclear.MethodsWe utilized our large-scale RNA-seq data on 655 patients with AML and the NAD metabolism-related genes to establish a prognostic NAD metabolism score based on the sparse regression analysis. The signature was validated across three independent datasets including a total of 1,215 AML patients. ssGSEA and ESTIMATE algorithms were employed to dissect the tumor immune microenvironment. Ex vivo drug screening and in vitro experimental validation were performed to identify potential therapeutic approaches for the high-risk patients. In vitro knockdown and functional experiments were employed to investigate the role of SLC25A51, a mitochondrial NAD+ transporter gene implicated in the signature.ResultsAn 8-gene NAD metabolism signature (NADM8) was generated and demonstrated a robust prognostic value in more than 1,800 patients with AML. High NADM8 score could efficiently discriminate AML patients with adverse clinical characteristics and genetic lesions and serve as an independent factor predicting a poor prognosis. Immune microenvironment analysis revealed significant enrichment of distinct tumor-infiltrating immune cells and activation of immune checkpoints in patients with high NADM8 scores, acting as a potential biomarker for immune response evaluation in AML. Furthermore, ex vivo drug screening and in vitro experimental validation in a panel of 9 AML cell lines demonstrated that the patients with high NADM8 scores were more sensitive to the PI3K inhibitor, GDC-0914. Finally, functional experiments also substantiated the critical pathogenic role of the SLC25A51 in AML, which could be a promising therapeutic target.ConclusionOur study demonstrated that NAD metabolism-related signature can facilitate risk stratification and prognosis prediction in AML and guide therapeutic decisions including both immunotherapy and targeted therapies.

Project description:BackgroundMetabolic reprogramming has been identified as a core hallmark of cancer. Solute carrier family 2 is a major glucose carrier family. It consists of 14 members, and we mainly study solute carrier family 2 member 1 (SLC2A1) and solute carrier family 2 member 2 (SLC2A2) here. SLC2A1, mainly existing in human erythrocytes, brain endothelial cells, and normal placenta, was found to be increased in hepatocellular carcinoma (HCC), while SLC2A2, the major transporter of the normal liver, was decreased in HCC.AimTo identify if SLC2A1 and SLC2A2 were associated with immune infiltration in addition to participating in the metabolic reprogramming in HCC.MethodsThe expression levels of SLC2A1 and SLC2A2 were tested in HepG2 cells, HepG215 cells, and multiple databases. The clinical characteristics and survival data of SLC2A1 and SLC2A2 were examined by multiple databases. The correlation between SLC2A1 and SLC2A2 was analyzed by multiple databases. The functions and pathways in which SLC2A1, SLC2A2, and frequently altered neighbor genes were involved were discussed in String. Immune infiltration levels and immune marker genes associated with SLC2A1 and SLC2A2 were discussed from multiple databases.ResultsThe expression level of SLC2A1 was up-regulated, but the expression level of SLC2A2 was down-regulated in HepG2 cells, HepG215 cells, and liver cancer patients. The expression levels of SLC2A1 and SLC2A2 were related to tumor volume, grade, and stage in HCC. Interestingly, the expression levels of SLC2A1 and SLC2A2 were negatively correlated. Further, high SLC2A1 expression and low SLC2A2 expression were linked to poor overall survival and relapse-free survival. SLC2A1, SLC2A2, and frequently altered neighbor genes played a major role in the occurrence and development of tumors. Notably, SLC2A1 was positively correlated with tumor immune infiltration, while SLC2A2 was negatively correlated with tumor immune infiltration. Particularly, SLC2A2 methylation was positively correlated with lymphocytes.ConclusionSLC2A1 and SLC2A2 are independent therapeutic targets for HCC, and they are quintessential marker molecules for predicting and regulating the number and status of immune cells in HCC.

Dataset Information

The Solute Carrier Family 2 Genes Are Potential Prognostic Biomarkers in Acute Myeloid Leukemia.

Publications

The Solute Carrier Family 2 Genes Are Potential Prognostic Biomarkers in Acute Myeloid Leukemia.

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