A novel stemness classification in acute myeloid leukemia by the stemness index and the identification of cancer stem cell-related biomarkers

摘要

BackgroundStem cells play an important role in acute myeloid leukemia (AML). However, their precise effect on AML tumorigenesis and progression remains unclear. MethodsThe present study aimed to characterize stem cell-related gene expression and identify stemness biomarker genes in AML. We calculated the stemness index (mRNAsi) based on transcription data using the one-class logistic regression (OCLR) algorithm for patients in the training set. According to the mRNAsi score, we performed consensus clustering and identified two stemness subgroups. Eight stemness-related genes were identified as stemness biomarkers through gene selection by three machine learning methods. ResultsWe found that patients in stemness subgroup I had a poor prognosis and benefited from nilotinib, MK-2206 and axitinib treatment. In addition, the mutation profiles of these two stemness subgroups were different, which suggested that patients in different subgroups had different biological processes. There was a strong significant negative correlation between mRNAsi and the immune score (r= -0.43, p<0.001). Furthermore, we identified eight stemness-related genes that have potential to be biomarkers, including SLC43A2, CYBB, CFP, GRN, CST3, TIMP1, CFD and IGLL1. These genes, except IGLL1, had a negative correlation with mRNAsi. SLC43A2 is expected to be a potential stemness-related biomarker in AML. ConclusionOverall, we established a novel stemness classification using the mRNAsi score and eight stemness-related genes that may be biomarkers. Clinical decision-making should be guided by this new signature in prospective studies.

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