Discovery and Identification of Potential Biomarkers of Pediatric Acute Lymphoblastic Leukemia

Overview

Journal Proteome Sci

Publisher Biomed Central

Date 2009 Mar 18

PMID 19291297

Citations 20

Authors

Linan Shi

Jun Zhang

Peng Wu

Kai Feng

Jing Li

Zhensheng Xie

Peng Xue

Tanxi Cai

Ziyou Cui

Xiulan Chen

Junjie Hou

Jianzhong Zhang

Fuquan Yang

Affiliations

Soon will be listed here.

Abstract

Background: Acute 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.

Methods: Ninety-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.

Results: A 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).

Conclusion: Platelet 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.

Citing Articles

Circulating Biomarkers Associated with the Diagnosis and Prognosis of B-Cell Progenitor Acute Lymphoblastic Leukemia.

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PMID: 37627214 PMC: 10453581. DOI: 10.3390/cancers15164186.

Biomarkers and Corresponding Biosensors for Childhood Cancer Diagnostics.

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Multifaceted Roles of Chemokine C-X-C Motif Ligand 7 in Inflammatory Diseases and Cancer.

Wu Q, Tu H, Li J Front Pharmacol. 2022; 13:914730.

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Assessment of Platelet Mitochondrial Respiration in a Pediatric Population: A Pilot Study in Healthy Children and Children with Acute Lymphoblastic Leukemia.

Lelcu T, Bina A, Danila M, Popoiu C, Aburel O, Arghirescu S Children (Basel). 2021; 8(12).

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Han Z, Wen L, Feng L Ann Transl Med. 2020; 8(18):1186.

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References

Sahu A, Lambris J . Structure and biology of complement protein C3, a connecting link between innate and acquired immunity. Immunol Rev. 2001; 180:35-48. DOI: 10.1034/j.1600-065x.2001.1800103.x. View

Qu Y, Adam B, Yasui Y, Ward M, Cazares L, Schellhammer P . Boosted decision tree analysis of surface-enhanced laser desorption/ionization mass spectral serum profiles discriminates prostate cancer from noncancer patients. Clin Chem. 2002; 48(10):1835-43. View

Adam B, Qu Y, Davis J, Ward M, Clements M, Cazares L . Serum protein fingerprinting coupled with a pattern-matching algorithm distinguishes prostate cancer from benign prostate hyperplasia and healthy men. Cancer Res. 2002; 62(13):3609-14. View

Ward D, Cheng Y, NKontchou G, Thar T, Barget N, Wei W . Changes in the serum proteome associated with the development of hepatocellular carcinoma in hepatitis C-related cirrhosis. Br J Cancer. 2006; 94(2):287-92. PMC: 2361123. DOI: 10.1038/sj.bjc.6602923. View

Petricoin E, Ardekani A, Hitt B, Levine P, Fusaro V, Steinberg S . Use of proteomic patterns in serum to identify ovarian cancer. Lancet. 2002; 359(9306):572-7. DOI: 10.1016/S0140-6736(02)07746-2. View

Bjorge L, Hakulinen J, Vintermyr O, Jarva H, Jensen T, Iversen O . Ascitic complement system in ovarian cancer. Br J Cancer. 2005; 92(5):895-905. PMC: 2361909. DOI: 10.1038/sj.bjc.6602334. View

Vlahou A, Schellhammer P, Mendrinos S, Patel K, Kondylis F, Gong L . Development of a novel proteomic approach for the detection of transitional cell carcinoma of the bladder in urine. Am J Pathol. 2001; 158(4):1491-502. PMC: 1891900. DOI: 10.1016/S0002-9440(10)64100-4. View

Chen G, Wang H, Gharib T, Huang C, Thomas D, Shedden K . Overexpression of oncoprotein 18 correlates with poor differentiation in lung adenocarcinomas. Mol Cell Proteomics. 2003; 2(2):107-16. DOI: 10.1074/mcp.M200055-MCP200. View

Pui C, Relling M, Downing J . Acute lymphoblastic leukemia. N Engl J Med. 2004; 350(15):1535-48. DOI: 10.1056/NEJMra023001. View

10.

Szekanecz Z, Koch A . Chemokines and angiogenesis. Curr Opin Rheumatol. 2001; 13(3):202-8. DOI: 10.1097/00002281-200105000-00009. View

11.

Paradis V, Degos F, Dargere D, Pham N, Belghiti J, Degott C . Identification of a new marker of hepatocellular carcinoma by serum protein profiling of patients with chronic liver diseases. Hepatology. 2005; 41(1):40-7. DOI: 10.1002/hep.20505. View

12.

Cazares L, Adam B, Ward M, Nasim S, Schellhammer P, John Semmes O . Normal, benign, preneoplastic, and malignant prostate cells have distinct protein expression profiles resolved by surface enhanced laser desorption/ionization mass spectrometry. Clin Cancer Res. 2002; 8(8):2541-52. View

13.

Parker S, Tong T, Bolden S, Wingo P . Cancer statistics, 1997. CA Cancer J Clin. 1997; 47(1):5-27. DOI: 10.3322/canjclin.47.1.5. View

14.

Zhukov T, Johanson R, Cantor A, Clark R, Tockman M . Discovery of distinct protein profiles specific for lung tumors and pre-malignant lung lesions by SELDI mass spectrometry. Lung Cancer. 2003; 40(3):267-79. DOI: 10.1016/s0169-5002(03)00082-5. View

15.

Lehrer S, ROBOZ J, Ding H, Zhao S, Diamond E, HOLLAND J . Putative protein markers in the sera of men with prostatic neoplasms. BJU Int. 2003; 92(3):223-5. DOI: 10.1046/j.1464-410x.2003.04341.x. View

16.

Strieter R, Belperio J, Phillips R, Keane M . Chemokines: angiogenesis and metastases in lung cancer. Novartis Found Symp. 2004; 256:173-84. View

17.

Melhem R, Hailat N, Kuick R, Hanash S . Quantitative analysis of Op18 phosphorylation in childhood acute leukemia. Leukemia. 1997; 11(10):1690-5. DOI: 10.1038/sj.leu.2400792. View

18.

Shiwa M, Nishimura Y, Wakatabe R, Fukawa A, Arikuni H, Ota H . Rapid discovery and identification of a tissue-specific tumor biomarker from 39 human cancer cell lines using the SELDI ProteinChip platform. Biochem Biophys Res Commun. 2003; 309(1):18-25. DOI: 10.1016/s0006-291x(03)01520-1. View

19.

Brattsand G . Correlation of oncoprotein 18/stathmin expression in human breast cancer with established prognostic factors. Br J Cancer. 2000; 83(3):311-8. PMC: 2374559. DOI: 10.1054/bjoc.2000.1264. View

20.

Pui C . Childhood leukemias. N Engl J Med. 1995; 332(24):1618-30. DOI: 10.1056/NEJM199506153322407. View