Advertisement

Molecular Biology Reports

, Volume 38, Issue 1, pp 631–638 | Cite as

Identification of novel serum biomarkers in child nephroblastoma using proteomics technology

  • Qian Zhang
  • Jiaxiang Wang
  • Rui Dong
  • Shaobo Yang
  • Shu Zheng
Article

Abstract

To screen and identify serum biomarkers for nephroblastoma in children using surface-enhanced laser desorption/ionization (SELDI) and other proteomics technologies. The surface-enhanced laser desorption/ionization time of flight mass spectrometry (SELDI–TOF-MS) was used to identify biomarkers in 100 children with nephroblastoma and 30 gender and age-matched normal healthy children. There were 30 cases of pre-operative patients and 70 cases of post-operative patients. Differentially expressed serum proteins were screened. The target proteins were then separated, purified, and analyzed by multidimensional high performance liquid chromatography (HPLC). The peptide mass fingerprints (PMFs) of each protein were obtained after scanning with LC-MS/MS (LTQ). The proteins were identified using SEQUEST and the biological functions and characterizations of these proteins were analyzed with bioinformatic methods. Two differential proteins (m/z 6455.5, 9190.8) were obtained. According to SEQUEST, the molecular masses of this two proteins indicated that they were apolipoprotein C-I and haptoglobin, respectively. Expressions of the two proteins were lower in the pre-surgery group compared with the post-surgery and control group (P < 0.01). In contrast, the expression of this two proteins were higher in the early stage than in the advanced stage of nephroblastoma. Apolipoprotein C-I and haptoglobin may be used as potential biomarkers to predict the degree of malignancy, therapeutic outcomes, and prognosis of nephroblastoma in children.

Keywords

Nephroblastoma Apolipoprotein C-I Haptoglobin SELDI–TOF-MS MALDI–TOF-MS 

Abbreviations

SELDI–TOF-MS

Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry

MALDI–TOF-MS

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry

HPLC

High performance liquid chromatography

PMFs

Peptide mass fingerprints

m/z

Mass-to-charge ratio

ApoC-I

Apolipoprotein C-I

Hp

Haptoglobin

SPA

Sinapinic acid

SVM

Support vector machine

CHCA

α-Cyanoacrylate-4-hydroxy-cinnamic acid

IAM

Iodine acetamide

Notes

Acknowledgement

This study was supported by National Natural Science Foundation of China (No. 30571930).

Supplementary material

11033_2010_149_MOESM1_ESM.doc (36 kb)
Supplementary material 1 (DOC 36 kb)

References

  1. 1.
    Hargrave DR et al (2001) Progressive reduction in treatment-related deaths in Medical Research Council childhood lymphoblastic leukaemia trials from 1980 to 1997 (UKALL VIII, X and XI). Br J Haematol 112(2):293–299CrossRefPubMedGoogle Scholar
  2. 2.
    Eden OB et al (2000) Long-term follow-up of the United Kingdom Medical Research Council protocols for childhood acute lymphoblastic leukaemia, 1980–1997. Medical Research Council Childhood Leukaemia Working Party. Leukemia 14(12):2307–2320CrossRefPubMedGoogle Scholar
  3. 3.
    McGregor LM et al (2007) Pediatric cancers in the new millennium: dramatic progress, new challenges. Oncology (Williston Park) 21(7): 809–820; discussion 820, 823–824Google Scholar
  4. 4.
    Rubnitz JE et al (2004) Death during induction therapy and first remission of acute leukemia in childhood: the St. Jude experience. Cancer 101(7):1677–1684CrossRefPubMedGoogle Scholar
  5. 5.
    Lawn JE, Cousens S, Zupan J (2005) 4 million neonatal deaths: when? Where? Why? Lancet 365(9462):891–900CrossRefPubMedGoogle Scholar
  6. 6.
    Miniati D et al (2008) Imaging accuracy and incidence of Wilms’ and non-Wilms’ renal tumors in children. J Pediatr Surg 43(7):1301–1307CrossRefPubMedGoogle Scholar
  7. 7.
    Lindor NM et al (2008) Concise handbook of familial cancer susceptibility syndromes—second edition. J Natl Cancer Inst Monogr 38:1–93PubMedGoogle Scholar
  8. 8.
    Ehrlich PF (2007) Wilms tumor: progress and considerations for the surgeon. Surg Oncol 16(3):157–171CrossRefPubMedGoogle Scholar
  9. 9.
    Medeiros LR et al (2009) Accuracy of CA 125 in the diagnosis of ovarian tumors: a quantitative systematic review. Eur J Obstet Gynecol Reprod Biol 142(2):99–105PubMedGoogle Scholar
  10. 10.
    Tsui KH et al (1997) Diagnosis of prostate cancer: comparison of serum prostate specific antigen, digital rectal examination and transrectal ultrasonography. Changgeng Yi Xue Za Zhi 20(1):23–28PubMedGoogle Scholar
  11. 11.
    Velaiutham S et al (2008) Does the pre-operative value of serum CA15-3 correlate with survival in breast cancer? Asian Pac J Cancer Prev 9(3):445–448PubMedGoogle Scholar
  12. 12.
    Zhong L, Taylor DL, Whittington RJ (2010) Proteomic profiling of ovine serum by SELDI-TOF MS: optimisation, reproducibility and feasibility of biomarker discovery using routinely collected samples. Comp Immunol Microbiol Infect Dis 33(1):47–63CrossRefPubMedGoogle Scholar
  13. 13.
    Wang J et al (2008) Proteomic studies of early-stage and advanced ovarian cancer patients. Gynecol Oncol 111(1):111–119CrossRefPubMedGoogle Scholar
  14. 14.
    Hong M et al (2009) The potential biomarkers for thromboembolism detected by SELDI-TOF-MS. Thromb Res 123(3):556–564CrossRefPubMedGoogle Scholar
  15. 15.
    Huang HL et al (2006) Biomarker discovery in breast cancer serum using 2-D differential gel electrophoresis/MALDI-TOF/TOF and data validation by routine clinical assays. Electrophoresis 27(8):1641–1650CrossRefPubMedGoogle Scholar
  16. 16.
    Song G, Ouyang G, Bao S (2005) The activation of Akt/PKB signaling pathway and cell survival. J Cell Mol Med 9(1):59–71CrossRefPubMedGoogle Scholar
  17. 17.
    Turner GA (1995) Haptoglobin. A potential reporter molecule for glycosylation changes in disease. Adv Exp Med Biol 376:231–238PubMedGoogle Scholar
  18. 18.
    Marinkovic S, Baumann H (1990) Structure, hormonal regulation, and identification of the interleukin-6- and dexamethasone-responsive element of the rat haptoglobin gene. Mol Cell Biol 10(4):1573–1583PubMedGoogle Scholar
  19. 19.
    Langlois MR, Delanghe JR (1996) Biological and clinical significance of haptoglobin polymorphism in humans. Clin Chem 42(10):1589–1600PubMedGoogle Scholar
  20. 20.
    Wassell J (2000) Haptoglobin: function and polymorphism. Clin Lab 46(11–12):547–552PubMedGoogle Scholar
  21. 21.
    Van Vlierberghe H, Langlois M, Delanghe J (2004) Haptoglobin polymorphisms and iron homeostasis in health and in disease. Clin Chim Acta 345(1–2):35–42CrossRefPubMedGoogle Scholar
  22. 22.
    Melamed-Frank M et al (2001) Structure-function analysis of the antioxidant properties of haptoglobin. Blood 98(13):3693–3698CrossRefPubMedGoogle Scholar
  23. 23.
    He Q, Zhang SQ, Chu YL et al (2009) The correlations between HPV16 infection and expressions of c-erbB-2 and bcl-2 in breast carcinoma. Mol Biol Rep 36(4):807–812CrossRefPubMedGoogle Scholar
  24. 24.
    Nakano M et al (2008) Site-specific analysis of N-glycans on haptoglobin in sera of patients with pancreatic cancer: a novel approach for the development of tumor markers. Int J Cancer 122(10):2301–2309CrossRefPubMedGoogle Scholar
  25. 25.
    Hoagland LF 4th et al (2007) Haptoglobin and posttranslational glycan-modified derivatives as serum biomarkers for the diagnosis of nonsmall cell lung cancer. Cancer 110(10):2260–2268CrossRefPubMedGoogle Scholar
  26. 26.
    Liu H, Zhang T, Wu B, Huang J, Zhou Y et al (2009) Chronic exposure to exogenous matrilysin induces chemoresistance and enhances Bcl-2 expression in A549 lung adenocarcinoma cells. Mol Biol Rep 36(8):2099–2109CrossRefPubMedGoogle Scholar
  27. 27.
    Fujimura T et al (2008) Glycosylation status of haptoglobin in sera of patients with prostate cancer vs. benign prostate disease or normal subjects. Int J Cancer 122(1):39–49CrossRefPubMedGoogle Scholar
  28. 28.
    Zhao C et al (2007) Circulating haptoglobin is an independent prognostic factor in the sera of patients with epithelial ovarian cancer. Neoplasia 9(1):1–7CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  • Qian Zhang
    • 1
  • Jiaxiang Wang
    • 1
  • Rui Dong
    • 1
  • Shaobo Yang
    • 1
  • Shu Zheng
    • 2
  1. 1.Department of Pediatric SurgeryFirst Affiliated Hospital of Zhengzhou UniversityZhengzhouChina
  2. 2.Cancer Institute of Zhejiang UniversityZhengzhouChina

Personalised recommendations