AUTHOR=Liu Fangshu , Deng Suqi , Li Yue , Du Juan , Zeng Hui 

TITLE=SLC25A1-associated prognostic signature predicts poor survival in acute myeloid leukemia patients

JOURNAL=Frontiers in Genetics

VOLUME=13

YEAR=2023

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2022.1081262

DOI=10.3389/fgene.2022.1081262

ISSN=1664-8021

ABSTRACT=<p><bold>Background:</bold> Acute myeloid leukemia (AML) is a heterogeneous malignant disease. <italic>SLC25A1</italic>, the gene encoding mitochondrial carrier subfamily of solute carrier proteins, was reported to be overexpressed in certain solid tumors. However, its expression and value as prognostic marker has not been assessed in AML.</p><p><bold>Methods:</bold> We retrieved RNA profile and corresponding clinical data of AML patients from the Beat AML, TCGA, and TARGET databases (TARGET_AML). Patients in the TCGA cohort were well-grouped into two group based on <italic>SLC25A1</italic> and differentially expressed genes were determined between the <italic>SLC25A1</italic> high and low group. The expression of <italic>SLC25A1</italic> was validated with clinical samples. The survival and apoptosis of two AML cell lines were analyzed with <italic>SLC25A1</italic> inhibitor (CTPI-2) treatment. Cox and the least absolute shrinkage and selection operator (LASSO) regression analyses were applied to Beat AML database to identify <italic>SLC25A1</italic>-associated genes for the construction of a prognostic risk-scoring model. Survival analysis was performed by Kaplan-Meier and receiver operator characteristic curves.</p><p><bold>Results:</bold> Our analysis revealed that high expressed level of <italic>SLC25A1</italic> in AML patients correlates with unfavorable prognosis. Moreover, <italic>SLC25A1</italic> expression was positively associated with metabolism activity. We further demonstrated that the inhibition of <italic>SLC25A1</italic> could inhibit the proliferation and increase the apoptosis of AML cells. In addition, a panel of <italic>SLC25A1</italic>-associated genes, was identified to construct a prognostic risk-scoring model. This <italic>SLC25A1</italic>-associated prognostic signature (SPS) is an independent risk factor with high area under curve (AUC) values of receiver operating characteristic (ROC) curves. A high SPS in leukemia patients is associated with poor survival. A Prognostic nomogram including the SPS and other clinical parameters, was constructed and its predictive efficiency was confirmed.</p><p><bold>Conclusion:</bold> We have successfully established a SPS prognostic model that predict outcome and risk stratification in AML. This risk model can be used as an independent biomarker to assess prognosis of AML.</p>