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A panel of glycoproteins as candidate biomarkers for early diagnosis and treatment evaluation of B-cell acute lymphoblastic leukemia

机译:一组糖蛋白作为B细胞急性淋巴细胞白血病的早期诊断和治疗评估的候选生物标志物

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BackgroundAcute lymphoblastic leukemia is the most common malignant cancer in childhood. The signs and symptoms of childhood cancer are difficult to recognize, as it is not the first diagnosis to be considered for nonspecific complaints, leading to potential uncertainty in diagnosis. The aim of this study was to perform proteomic analysis of serum from pediatric patients with B-cell acute lymphoblastic leukemia (B-ALL) to identify candidate biomarker proteins, for use in early diagnosis and evaluation of treatment. MethodsSerum samples were obtained from ten patients at the time of diagnosis (B-ALL group) and after induction therapy (AIT group). Sera from healthy children were used as controls (Control group). The samples were subjected to immunodepletion, affinity chromatography with α- d -galactose-binding lectin (from Artocarpus incisa seeds) immobilized on a SepharoseTM 4B gel, concentration, and digestion for subsequent analysis with nano-UPLC tandem nano-ESI-MSE. The program Expression E was used to quantify differences in protein expression between groups. ResultsA total of 96 proteins were identified. Leucine-rich alpha-2-glycoprotein 1 (LRG1), Clusterin (CLU), thrombin (F2), heparin cofactor II (SERPIND1), alpha-2-macroglobulin (A2M), alpha-2-antiplasmin (SERPINF2), Alpha-1 antitrypsin (SERPINA1), Complement factor B (CFB) and Complement C3 (C3) were identified as candidate biomarkers for early diagnosis of B-ALL, as they were upregulated in the B-ALL group relative to the control and AIT groups. Expression levels of the candidate biomarkers did not differ significantly between the AIT and control groups, providing further evidence that the candidate biomarkers are present only in the disease state, as all patients achieved complete remission after treatment. ConclusionA panel of protein biomarker candidates has been developed for pre-diagnosis of B-ALL and also provided information that would indicate a favorable response to treatment after induction therapy.
机译:背景急性淋巴细胞白血病是儿童期最常见的恶性肿瘤。儿童癌症的体征和症状难以识别,因为它不是针对非特异性主诉的第一种诊断方法,从而导致诊断的不确定性。这项研究的目的是对患有B细胞急性淋巴细胞白血病(B-ALL)的小儿患者的血清进行蛋白质组学分析,以鉴定候选生物标志物蛋白,以用于早期诊断和评估治疗。方法:从诊断时(B-ALL组)和诱导治疗后(AIT组)的十名患者获得血清样本。健康儿童的血清用作对照组(对照组)。对样品进行免疫耗竭,用固定在Sepharose 4B凝胶上的α-d-半乳糖结合凝集素(来自面包果种子)进行亲和层析,浓缩,并消解,以用于随后的Nano-UPLC分析串联纳米ESI-MS E 。程序Expression E 用于量化组之间蛋白质表达的差异。结果共鉴定出96种蛋白质。富含亮氨酸的α-2-糖蛋白1(LRG1),簇蛋白(CLU),凝血酶(F2),肝素辅因子II(SERPIND1),α-2-巨球蛋白(A2M),α-2-抗纤溶酶(SERPINF2),α- 1种抗胰蛋白酶(SERPINA1),补体因子B(CFB)和补体C3(C3)被鉴定为B-ALL早期诊断的候选生物标志物,因为相对于对照组和AIT组,它们在B-ALL组中上调。候选生物标志物的表达水平在AIT组和对照组之间没有显着差异,这提供了进一步的证据,表明候选生物标志物仅以疾病状态存在,因为所有患者均在治疗后完全缓解。结论已经开发出一组蛋白质生物标志物候选物用于B-ALL的预诊断,并且还提供了表明诱导治疗后对治疗反应良好的信息。

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