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基于TMT的综合蛋白质组学分析鉴定急性髓系白血病的血清预后标志物。

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

作者信息

Zhang Wei, Liu Bei, Wu Shiwen, Zhao Li

机构信息

Department of Central Laboratory, The First Hospital of Lanzhou University, Lanzhou 730000, Gansu Province, China.

Department of Hematology, The First Hospital of Lanzhou University, Lanzhou 730000, China.

出版信息

Open Med (Wars). 2023 Mar 30;18(1):20220602. doi: 10.1515/med-2022-0602. eCollection 2023.

DOI:10.1515/med-2022-0602
PMID:37016705
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10066874/
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 ( = 14), intermediate-risk ( = 19), and poor-risk AMLs ( = 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, = 0.010), glutamine synthetase (GLUL, OR = 1.022, = 0.039), and lactotransferrin (LTF, OR = 1.1224, = 0.016) were associated with poor prognosis, and proteins ENO1 (OR = 1.154, = 0.053), FH (OR = 1.043, = 0.059), and IDH2 (OR = 3.350, = 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.

摘要

急性髓系白血病(AML)分为低危、中危和高危亚型。本研究旨在比较三种AML亚型的血清蛋白质组学特征,并鉴定AML的预后生物标志物。收集低危(n = 14)、中危(n = 19)和高危AML患者(n = 18)的血清样本,用于基于串联质谱标签(TMT)标记的定量蛋白质组学分析。进行比较分析以鉴定组间差异表达蛋白(DEP)。使用二元逻辑回归分析筛选预后蛋白。TMT-MS/MS蛋白质组学分析鉴定出138个DEP。与低危患者相比,高危患者中延胡索酸水合酶(FH)、异柠檬酸脱氢酶2(IDH2)和烯醇化酶1(ENO1)显著上调。酶联免疫吸附测定(ELISA)证实,与中危AML患者相比,高危AML患者的IDH2、ENO1和FH水平更高。逻辑分析确定,2型3-羟酰基辅酶A脱氢酶(HADH,比值比(OR)= 1.035,P = 0.010)、谷氨酰胺合成酶(GLUL,OR = 1.022,P = 0.039)和乳铁传递蛋白(LTF,OR = 1.1224,P = 0.016)与预后不良相关,而ENO1(OR = 1.154,P = 0.053)、FH(OR = 1.043,P = 0.059)和IDH2(OR = 3.350,P = 0.055)与AML预后相关。本研究表明,AML患者的FH、IDH2、ENO1、LTF和GLUL蛋白水平升高,可能预后不良风险较高。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5221/10066874/88b8acfd1aa8/j_med-2022-0602-fig004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5221/10066874/1246e0c28b43/j_med-2022-0602-fig001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5221/10066874/9733cebc6f42/j_med-2022-0602-fig002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5221/10066874/3ab0510f1ab8/j_med-2022-0602-fig003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5221/10066874/88b8acfd1aa8/j_med-2022-0602-fig004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5221/10066874/1246e0c28b43/j_med-2022-0602-fig001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5221/10066874/9733cebc6f42/j_med-2022-0602-fig002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5221/10066874/3ab0510f1ab8/j_med-2022-0602-fig003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5221/10066874/88b8acfd1aa8/j_med-2022-0602-fig004.jpg

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