Abstract
BackgroundAcute lymphoblastic leukemia (ALL) is a common form of cancer in children. Currently, bone marrow biopsy is used for diagnosis. Noninvasive biomarkers for the early diagnosis of pediatric ALL are urgently needed. The aim of this study was to discover potential protein biomarkers for pediatric ALL.MethodsNinety-four pediatric ALL patients and 84 controls were randomly divided into a "training" set (45 ALL patients, 34 healthy controls) and a test set (49 ALL patients, 30 healthy controls and 30 pediatric acute myeloid leukemia (AML) patients). Serum proteomic profiles were measured using surface-enhanced laser desorption/ionization-time-of-flight mass spectroscopy (SELDI-TOF-MS). A classification model was established by Biomarker Pattern Software (BPS). Candidate protein biomarkers were purified by HPLC, identified by LC-MS/MS and validated using ProteinChip immunoassays.ResultsA total of 7 protein peaks (9290 m/z, 7769 m/z, 15110 m/z, 7564 m/z, 4469 m/z, 8937 m/z, 8137 m/z) were found with differential expression levels in the sera of pediatric ALL patients and controls using SELDI-TOF-MS and then analyzed by BPS to construct a classification model in the "training" set. The sensitivity and specificity of the model were found to be 91.8%, and 90.0%, respectively, in the test set. Two candidate protein peaks (7769 and 9290 m/z) were found to be down-regulated in ALL patients, where these were identified as platelet factor 4 (PF4) and pro-platelet basic protein precursor (PBP). Two other candidate protein peaks (8137 and 8937 m/z) were found up-regulated in the sera of ALL patients, and these were identified as fragments of the complement component 3a (C3a).ConclusionPlatelet factor (PF4), connective tissue activating peptide III (CTAP-III) and two fragments of C3a may be potential protein biomarkers of pediatric ALL and used to distinguish pediatric ALL patients from healthy controls and pediatric AML patients. Further studies with additional populations or using pre-diagnostic sera are needed to confirm the importance of these findings as diagnostic markers of pediatric ALL.
Highlights
Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer, accounting for 30% of all pediatric malignancies [1]
Serum protein profiles and data processing All the serum samples were collected from the selected patients and controls in 2004, distributed into 20 mL per tube, and stored at -80°C until use
The results indicated that two protein peaks (8137 m/z, p value 6.07E-05 and 8937 m/z, p value 5.13E-05) were up-regulated in sera from ALL patients, while two other peaks (7769 m/z, p value 1.54E-07 and 9290 m/z, p value 7.59E-08) were down-regulated, compared with those from the healthy controls
Summary
Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer, accounting for 30% of all pediatric malignancies [1]. Melhem reported that oncoprotein 18 (Op18) phosphorylation was significantly correlated with the white blood cell count and the percentage of cells in S phase [7]. Brattsand and Chen reported that over-phosphorylation of Op18 was found in breast cancer and lung adenocarcinomas [8,9]. Noninvasive and specific biomarkers for early diagnoses of pediatric ALL remain an urgent need. Acute lymphoblastic leukemia (ALL) is a common form of cancer in children. Noninvasive biomarkers for the early diagnosis of pediatric ALL are urgently needed. The aim of this study was to discover potential protein biomarkers for pediatric ALL
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