Clinical Chemistry
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Clinical Chemistry 53: 241-250, 2007. First published January 2, 2007; 10.1373/clinchem.2005.065805
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(Clinical Chemistry. 2007;53:241-250.)
© 2007 American Association for Clinical Chemistry, Inc.

Cancer Diagnostics

ProteinChip Array Profiling for Identification of Disease- and Chemotherapy-Associated Biomarkers of Nasopharyngeal Carcinoma

William C.S. Cho1, Timothy T.C. Yip1,a, Roger K.C. Ngan1,a, Tai-Tung Yip2, Vladimir N. Podust2, Christine Yip2, Harry H.Y. Yiu1, Victor Yip2, Wai-Wai Cheng1, Victor W.S. Ma1 and Stephen C.K. Law1

1 Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong Special Administrative Region, The People’s Republic of China.
2 Ciphergen Biosystems Inc., Fremont, CA.

aAddress correspondence to these authors at: Dr. Roger K.C. Ngan or Dr. Timothy T.C. Yip, Department of Clinical Oncology, Queen Elizabeth Hospital, 30, Gascoigne Road, Kowloon, Hong Kong SAR. Fax 852-23594782 or 852-29585455; e-mail ngankc{at}ha.org.hk or yiptc{at}ha.org.hk.

Background: We previously used ProteinChip array profiling analysis to discover a serum biomarker associated with nasopharyngeal carcinoma (NPC). In this study, we used the same method to examine other biomarkers associated with NPC and response to chemotherapy (CT) in NPC patients.

Methods: We performed ProteinChip array analysis in 209 serum samples from 66 relapsed patients before and after salvage CT with gemcitabine and cisplatin or etoposide and cisplatin combinations, 11 patients in remission, and 35 healthy individuals. Intensities of the biomarker peaks were correlated with CT response of the patients and other clinical parameters.

Results: We discovered 13 candidate biomarkers associated with different clinical parameters. Two biomarkers (2803 and 3953 Da) were significantly increased in patients compared with controls at all stages of disease. Analysis of pre- and post-CT paired serum samples revealed 7 biomarkers correlated with impact of CT. Of these 7 biomarkers, 2 (2509 and 2756 Da) were significantly increased and 5 (7588, 7659, 7765, 7843, and 8372 Da) were significantly decreased post-CT in either 1 or both CT cohorts. Four biomarkers from pre-CT sera were correlated with CT response, with 3 (2950, 13 510, and 14 855 Da) being significantly decreased and 1 (6701 Da) significantly increased in patients who did not respond to CT. Tandem mass spectrometric sequencing and/or immunoaffinity capture assay identified the 3953 Da biomarker as a fragment of inter{alpha}-trypsin inhibitor precursor and 7765 Da biomarker as platelet factor-4.

Conclusions: Treatment-associated serum biomarkers found might serve to triage NPC patients for appropriate CT treatment.






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