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

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.

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Abstract 3540: Down-regulation of solute carrier family 17 member 1(SLC17A1) expression contributes to chemotherapy resistance in acute myeloid leukemia

10.1158/1538-7445.am10-3540 ◽

2010 ◽

Author(s):

Chansu Lee ◽

Juwon Park ◽

Jeong In Oh ◽

Byung-Su Kim ◽

Jung Hye Kwon ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Chemotherapy Resistance ◽

Solute Carrier Family ◽

Down Regulation ◽

Solute Carrier ◽

Acute Myeloid

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Identification of Prognostic Signature Based on the Copy Number Variation (CNV) and Expression in Acute Myeloid Leukemia

10.21203/rs.3.rs-64413/v1 ◽

2020 ◽

Author(s):

Changchun Niu ◽

Di Wu ◽

Alexander J. Li ◽

Kevin H. Qin ◽

Daniel A. Hu ◽

...

Keyword(s):

Gene Expression ◽

Acute Myeloid Leukemia ◽

Survival Analysis ◽

Copy Number Variation ◽

Copy Number ◽

Myeloid Leukemia ◽

Risk Groups ◽

Number Variation ◽

Acute Myeloid ◽

Cancer Panel

Abstract Purpose Acute myeloid leukemia (AML) is caused by multiple genetic alterations in the hematopoietic progenitors, and molecular genetic analysis has provided useful information for AML diagnosis and prognosis. However, an integrative understanding about the prognosis value of specific copy number variation (CNV) and CNV-modulated gene expression has been limited. Methods We conducted an integrative analysis of CNV profiling and gene expression using data from the TARGET and TCGA AML cohorts. The CNV data from TCGA were analyzed using the GISTIC. CNV survival analysis and mRNA survival analysis were conducted with the Multivariate Cox proportional hazards regression model using R software with “survminer” and “survival” packages. KEGG cancer panel genes were extracted from the cancer related pathways from Kyoto Encyclopedia of Genes and Genomes (KEGG). The R package “circlize” was used for mapping the CNV genes to chromosomes. Results From this investigation, we observed distinct CNV patterns in the AML risk groups as well as the expression of 251 genes significantly modulated by CNV in both cohorts. There were 102 CNV genes (located at 7q31-34, 16q24) associated with clinical outcomes in AML, which were identified in the TARGET cohort and validated in the TCGA cohort, three of which being miRNA genes (MIR29A, MIR183, MIR335) that overlapped with a KEGG cancer panel. Five genes were identified whose expressions were modulated by CNV and significantly associated with clinical outcomes, and among them, the deletion of SEMA4D and CBFB were found to potentially have protective effects against AML. Moreover, the distribution of CNV in these five CNV-modulated genes was independent of the risk groups, which suggests that they are independent prognosis factors. Conclusion Overall, this study identified 102 CNV genes and five CNV-modulated gene expressions that are crucial for developing new modes of prognosis evaluation and target therapy for AML.

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Identification of prognostic signature based on the copy number variation (CNV) and expression in acute myeloid leukemia

10.21203/rs.3.rs-64413/v2 ◽

2021 ◽

Author(s):

Changchun Niu ◽

Di Wu ◽

Alexander J. Li ◽

Kevin H. Qin ◽

Daniel A. Hu ◽

...

Keyword(s):

Gene Expression ◽

Acute Myeloid Leukemia ◽

Survival Analysis ◽

Copy Number Variation ◽

Copy Number ◽

Myeloid Leukemia ◽

Risk Groups ◽

Number Variation ◽

Acute Myeloid ◽

Cancer Panel

Abstract Background Acute myeloid leukemia (AML) is caused by multiple genetic alterations in the hematopoietic progenitors, and molecular genetic analysis has provided useful information for AML diagnosis and prognosis. However, an integrative understanding of the prognostic value of specific copy number variation (CNV) and CNV-modulated gene expression has been limited. Methods We conducted an integrative analysis of CNV profiling and gene expression using data from the TARGET and TCGA AML cohorts. The CNV data from TCGA were analyzed using the GISTIC and all CNV data by genes on every patient were obtained. CNV survival analysis and mRNA survival analysis were conducted with the Multivariate Cox proportional hazards regression model using R software with “survminer” and “survival” packages. KEGG cancer panel genes were extracted from the cancer-related pathways from Kyoto Encyclopedia of Genes and Genomes (KEGG). The R package “circlize” was used for mapping the CNV genes to chromosomes. Results From this investigation, we observed distinct CNV patterns in the AML risk groups as well as the expression of 251 genes significantly modulated by CNV in both cohorts. There were 102 CNV genes (located at 7q31-34, 16q24) associated with clinical outcomes in AML, which were identified in the TARGET cohort and validated in the TCGA cohort, three of which being miRNA genes (MIR29A, MIR183, MIR335) that overlapped with a KEGG cancer panel. Five genes were identified whose expression was modulated by CNV and significantly associated with clinical outcomes, and among them, the deletion of SEMA4D and CBFB were found to potentially have protective effects against AML. The result was also validated with patient marrow samples. Moreover, the distribution of CNV in these five CNV-modulated genes was independent of the risk groups, which suggests that they are independent prognosis factors. Conclusion Overall, this study identified 102 CNV genes and five CNV-modulated gene expression that is crucial for developing new modes of prognosis evaluation and target therapy for AML.

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Risk stratification of intermediate-risk acute myeloid leukemia: integrative analysis of a multitude of gene mutation and gene expression markers

Blood ◽

10.1182/blood-2011-02-334748 ◽

2011 ◽

Vol 118 (4) ◽

pp. 1069-1076 ◽

Cited By ~ 79

Author(s):

Veronika Rockova ◽

Saman Abbas ◽

Bas J. Wouters ◽

Claudia A. J. Erpelinck ◽

H. Berna Beverloo ◽

...

Keyword(s):

Gene Expression ◽

Acute Myeloid Leukemia ◽

Survival Analysis ◽

Myeloid Leukemia ◽

Intermediate Risk ◽

Free Survival ◽

Intermediate Group ◽

Prognostic Importance ◽

Survival Tree ◽

Acute Myeloid

Abstract Numerous molecular markers have been recently discovered as potential prognostic factors in acute myeloid leukemia (AML). It has become of critical importance to thoroughly evaluate their interrelationships and relative prognostic importance. Gene expression profiling was conducted in a well-characterized cohort of 439 AML patients (age < 60 years) to determine expression levels of EVI1, WT1, BCL2, ABCB1, BAALC, FLT3, CD34, INDO, ERG and MN1. A variety of AML-specific mutations were evaluated, that is, FLT3, NPM1, N-RAS, K-RAS, IDH1, IDH2, and CEBPADM/SM (double/single). Univariable survival analysis shows that (1) patients with FLT3ITD mutations have inferior overall survival (OS) and event-free survival (EFS), whereas CEBPADM and NPM1 mutations indicate favorable OS and EFS in intermediate-risk AML, and (2) high transcript levels of BAALC, CD34, MN1, EVl1, and ERG predict inferior OS and EFS. In multivariable survival analysis, CD34, ERG, and CEBPADM remain significant. Using survival tree and regression methodologies, we show that CEBPADM, CD34, and IDH2 mutations are capable of separating the intermediate group into 2 AML subgroups with highly distinctive survival characteristics (OS at 60 months: 51.9% vs 14.9%). The integrated statistical approach demonstrates that from the multitude of biomarkers a greatly condensed subset can be selected for improved stratification of intermediate-risk AML.

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