Colorectal Cancer
Copyright ©2006 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Mar 14, 2006; 12(10): 1536-1544
Published online Mar 14, 2006. doi: 10.3748/wjg.v12.i10.1536
Identification of serum proteins discriminating colorectal cancer patients and healthy controls using surface-enhanced laser desorption ionisation-time of flight mass spectrometry
Judith YMN Engwegen, Helgi H Helgason, Annemieke Cats, Nathan Harris, Johannes MG Bonfrer, Jan HM Schellens, Jos H Beijnen
Judith YMN Engwegen, Jos H Beijnen, Department of Pharmacy and Pharmacology, The Netherlands Cancer Institute/Slotervaart Hospital, Amsterdam, The Netherlands
Helgi H Helgason, Jan HM Schellens, Department of Medical Oncology, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
Annemieke Cats, Department of Gastroenterology and Hepatology, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
Nathan Harris, Ciphergen Biosystems Inc., Freemont, California, United States
Johannes MG Bonfrer, Department of Clinical Chemistry, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
Jan HM Schellens, Jos H Beijnen, Utrecht University, Faculty of Pharmaceutical Sciences, Department of Biomedical analysis, Utrecht, The Netherlands
Author contributions: All authors contributed equally to the work.
Correspondence to: Judith YMN Engwegen, Slotervaart Hospital, Department of Pharmacy and Pharmacology, PO Box 90440, 1006 BK Amsterdam, The Netherlands.
Telephone: +31-20-5125008 Fax: +31-20-5124753
Received: June 23, 2005
Revised: September 1, 2005
Accepted: October 9, 2005
Published online: March 14, 2006

AIM: To detect the new serum biomarkers for colorectal cancer (CRC) by serum protein profiling with surface-enhanced laser desorption ionisation - time of flight mass spectrometry (SELDI-TOF MS).

METHODS: Two independent serum sample sets were analysed separately with the ProteinChip technology (set A: 40 CRC + 49 healthy controls; set B: 37 CRC + 31 healthy controls), using chips with a weak cation exchange moiety and buffer pH 5. Discriminative power of differentially expressed proteins was assessed with a classification tree algorithm. Sensitivities and specificities of the generated classification trees were obtained by blindly applying data from set A to the generated trees from set B and vice versa. CRC serum protein profiles were also compared with those from breast, ovarian, prostate, and non-small cell lung cancer.

RESULTS: Mass-to-charge ratios (m/z) 3.1×103, 3.3×103, 4.5×103, 6.6×103 and 28×103 were used as classifiers in the best-performing classification trees. Tree sensitivities and specificities were between 65% and 90%. Most of these discriminative m/z values were also different in the other tumour types investigated. M/z 3.3×103, main classifier in most trees, was a doubly charged form of the 6.6×103-Da protein. The latter was identified as apolipoprotein C-I. M/z 3.1×103 was identified as an N-terminal fragment of albumin, and m/z 28×103 as apolipoprotein A-I.

CONCLUSION: SELDI-TOF MS followed by classification tree pattern analysis is a suitable technique for finding new serum markers for CRC. Biomarkers can be identified and reproducibly detected in independent sample sets with high sensitivities and specificities. Although not specific for CRC, these biomarkers have a potential role in disease and treatment monitoring.

Keywords: Proteomics, Colorectal cancer, Biomarker, Sensitivity, Specificity