Proteome Changes in the Plasma of Myelodysplastic Syndrome Patients with Refractory Anemia with Excess Blasts Subtype 2

Abstract

The goal of this study was to explore the plasma proteome of myelodysplastic syndrome (MDS) patients with refractory anemia with excess blasts subtype 2 (RAEB-2) in comparison to healthy controls. 20 plasma samples were separated with 2D electrophoresis and statistically processed with Progenesis SameSpots software. 47 significantly differing (P < 0.05) spots were observed, and 27 different proteins were identified by nano-LC-MS/MS. Mass spectrometry-based relative label-free quantification showed a 2-fold increase of the leucine-rich alpha-2-glycoprotein (LRAG) peptide levels in the RAEB-2 group. Changes in the fragments of the inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4) protein were observed. Western blot analysis showed no differences in albumin and ITIH4 levels, while increased expression was observed for LRAG in the RAEB-2 group. Quantification using ELISA showed decreased plasma level of alpha-2-HS glycoprotein in the RAEB-2 group. In conclusion, this is the first time that alpha-2-HS glycoprotein and LRAG were proposed as new biomarkers of RAEB-2 and advanced MDS, respectively. Alpha-2-HS glycoprotein, a protein involved in the bone marrow development and previously proposed as a MDS biomarker candidate, was significantly decreased in RAEB-2. Increased expression and changes in modification(s) were observed for LRAG, a protein involved in granulocytic and neutrophil differentiation, and angiogenesis.

Leucine Rich α-2 Glycoprotein: A Novel Neutrophil Granule Protein and Modulator of Myelopoiesis

“…Subsequent studies have shown that LRG1 expression increases in hepatocytes in response to mediators of the acute-phase response, and serum LRG1 levels are increased in patients with bacterial infections [3, 4]. Increased concentrations of LRG1 have also been observed in a variety of neoplastic and inflammatory disorders, prompting a number of investigators to suggest that LRG1 is a biomarker of these diseases [5–8]. Additionally, our group previously reported that transcription of LRG1 is upregulated in myeloid cells during granulopoiesis and ectopic overexpression of LRG1 accelerates granulopoiesis in vitro , suggesting a role for LRG1 in myeloid cell maturation [9].…”

Alterations of the Plasma Peptidome Profiling in Colorectal Cancer Progression

“…The remained 100 kDa peptide undergoes to a second cleavage to produce the 70kDa peptide and the [662–688] pro‐peptide containing the proline‐rich region ([658–688] PRR domain). The [669–688] fragment had been observed in thyroid metastatic and bladder, prostate, and breast cancer in the Villanueva and co‐authors’ studies (Villanueva et al, ; Karpova et al, ), while different fragmentation patterns were associated to several pathologies such as recurrent pregnancy loss (Kim et al, ), myelodysplastic syndrome (Majek et al, ), kidney (Gianazza et al, ), breast (van den Broek et al, ), ovarian, prostate, and pancreas cancer and diabetic disease (Song et al, ). Many tumors present a different proteolytic pattern of ITIH4 PRR domain, thus the pro‐peptide could be potentially bioactive peptide and its fragmentation pattern could keep important diagnostic or prognostic information to be studied.…”

Prospective plasma proteome changes in preterm infants with different gestational ages

“…Importantly, LRG1 induction has been considered a biomarker of several neoplastic and inflammatory disorders. 26,27 The production of LRG1 increases in response to mediators of the acute-phase response, while serum LRG1 levels are elevatehrough by its secretion from activated neutrophils. 28 Additionally, we identified gelsolin as being differentially regulated in the 36-PMA samples, and this molecule was decreased in abundance in all three groups of preterm neonates, with a fold-change of approximately −1.4 ( Table 2).…”