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. 2016 Jan 27:4:1.
doi: 10.1186/s40364-016-0055-6. eCollection 2016.

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

Marcio de Souza Cavalcante  1 , José Camilo Torres-Romero  2 , Marina Duarte Pinto Lobo  2 , Frederico Bruno Mendes Batista Moreno  3 , Leonardo Primo Bezerra  3 , Diego Silva Lima  4 , Jesamar Correia Matos  5 , Renato de Azevedo Moreira  3 , Ana Cristina de Oliveira Monteiro-Moreira  3
Affiliations

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

Marcio de Souza Cavalcante et al. Biomark Res. .

Abstract

Background: Acute 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.

Methods: Serum 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 Sepharose(TM) 4B gel, concentration, and digestion for subsequent analysis with nano-UPLC tandem nano-ESI-MS(E). The program Expression (E) was used to quantify differences in protein expression between groups.

Results: A 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.

Conclusion: A 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.

Keywords: Acute lymphoblastic leukemia; Biomarker; Frutalin; Lectin; Mass spectrometry.

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Figures

Fig. 1
Fig. 1
Graphical representation of the affinity chromatography process on a Frutalin-immobilized column with Sepharose 4B, coupled with an ÄKTA purifier 10 FPLC system. Peak I represents the non-retained fraction (FNR) and Peak II represents the retained fraction (FR). The fractions were obtained after elution with their respective buffers: 20 mM Tris–HCl, pH 7.4, in0.15 M NaCl (Buffer A) and 0.2 M galactose and 20 mM Tris–HCl, pH 7.4, in 0.15 M NaCl (Buffer B). The blue line represents absorbance at 280 nm and the red represents emission at 216 nm
Fig. 2
Fig. 2
Panel of candidate protein biomarkers for B-ALL. Blue columns represent the expression levels of the proteins in B-ALL patients at the time of diagnosis in relation to the control. Green columns represent the expression levels of the proteins in B-ALL patients after induction therapy (day 35) relative to controls. (*) (p < 0.05)
Fig. 3
Fig. 3
Interactome generated by STRING interaction database. Required confidence (score): medium confidence (0.400)
See this image and copyright information in PMC

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