TMT-based comprehensive proteomic profiling identifies serum prognostic signatures of acute myeloid leukemia

Abstract

Acute myeloid leukemia (AML) is classified into favorable-risk, intermediate-risk, and poor-risk subtypes. This study aimed to compare the serum proteomic signatures of the three AML subtypes and identify prognostic biomarkers for AML. Serum samples from patients with favorable-risk (n = 14), intermediate-risk (n = 19), and poor-risk AMLs (n = 18) were used for the analysis of tandem mass tag (TMT) labeling-based quantitative proteomics. Comparative analysis was performed to identify differentially expressed proteins (DEPs) between groups. Prognostic proteins were screened using binary logistics regression analysis. TMT-MS/MS proteomics analysis identified 138 DEPs. Fumarate hydratase (FH), isocitrate dehydrogenase 2 (IDH2), and enolase 1 (ENO1) were significantly upregulated in poor-risk patients compared with favorable-risk patients. ELISA assay confirmed that patients with poor-risk AMLs had higher levels of IDH2, ENO1, and FH compared with intermediate-risk AML patients. Logistics analysis identified that proteins 3-hydroxyacyl-CoA dehydrogenase type-2 (HADH, odds ratio (OR) = 1.035, p = 0.010), glutamine synthetase (GLUL, OR = 1.022, p = 0.039), and lactotransferrin (LTF, OR = 1.1224, p = 0.016) were associated with poor prognosis, and proteins ENO1 (OR = 1.154, p = 0.053), FH (OR = 1.043, p = 0.059), and IDH2 (OR = 3.350, p = 0.055) were associated with AML prognosis. This study showed that AML patients had elevated levels of FH, IDH2, ENO1, LTF, and GLUL proteins and might be at high risk of poor prognosis.

Keywords

• tmt labeling-based quantitative proteomics
• isocitrate dehydrogenase 2
• favorable-risk acute myeloid leukemia
• prognostic biomarker
• proteomic profiling