Discovery of diagnostic biomarkers for pancreatic cancer in immunodepleted serum by SELDI-TOF MS.

ABSTRACT

MOTIVATION Reports of serum pancreatic cancer (PC) biomarkers using SELDI-TOF MS have been inconsistent because different chip surfaces and interference with high-abundant proteins. This study examines the influence of these factors on the detection of discriminating diagnostic biomarkers. METHODS: Serum from fourteen from patients with PC, disease controls (DC, n = 14) and healthy volunteers (HV, n = 14) were evaluated by SELDI using H50, IMAC, Q10 and CM10 chips. A further evaluation was undertaken after depletion of seven high-abundant proteins using spin cartridges. RESULTS: More protein peaks were detected in whole serum than in depleted serum for IMAC, H50 and Q10 chips 60 vs 39, 56 vs 48 and 69 vs 65, respectively, while the CM10 found less peaks in serum (27 vs 47 peaks). However, there were more differentially expressed peaks in the depleted serum samples for PC vs DC and PC vs HV samples using the H50, Q10 and CM10 ProteinChip arrays, whereas for IMAC arrays, more discriminating peaks were seen in non-depleted serum. The highly significant peaks observed on Q10, CM10 and H50 are consistent with the previous finding of ApoA-I (m/z 27,910-28000) and ApoA-II (m/z 8758 and 17,240). In addition, a number of new discriminating protein peaks were found on different ProteinChip arrays, notably peaks at m/z 4280 and 7763 on IMAC arrays. CONCLUSION: This study confirms the diagnostic value of ApoA-I&II and identifies further potential diagnostic biomarkers for pancreatic cancer when multiple chip surfaces are used with depletion of the most highly-abundant proteins.