Peptides generated ex vivo from serum proteins by tumor-specific exopeptidases are not useful biomarkers in ovarian cancer.
BACKGROUND
The serum peptidome may be a valuable source of diagnostic cancer biomarkers. Previous mass spectrometry (MS) studies have suggested that groups of related peptides discriminatory for different cancer types are generated ex vivo from abundant serum proteins by tumor-specific exopeptidases. We tested 2 complementary serum profiling strategies to see if similar peptides could be found that discriminate ovarian cancer from benign cases and healthy controls.


METHODS
We subjected identically collected and processed serum samples from healthy volunteers and patients to automated polypeptide extraction on octadecylsilane-coated magnetic beads and separately on ZipTips before MALDI-TOF MS profiling at 2 centers. The 2 platforms were compared and case control profiling data analyzed to find altered MS peak intensities. We tested models built from training datasets for both methods for their ability to classify a blinded test set.


RESULTS
Both profiling platforms had CVs of approximately 15% and could be applied for high-throughput analysis of clinical samples. The 2 methods generated overlapping peptide profiles, with some differences in peak intensity in different mass regions. In cross-validation, models from training data gave diagnostic accuracies up to 87% for discriminating malignant ovarian cancer from healthy controls and up to 81% for discriminating malignant from benign samples. Diagnostic accuracies up to 71% (malignant vs healthy) and up to 65% (malignant vs benign) were obtained when the models were validated on the blinded test set.


CONCLUSIONS
For ovarian cancer, altered MALDI-TOF MS peptide profiles alone cannot be used for accurate diagnoses.
Timms
John F
JF
Institute for Women's Health, University College London, London, UK.
Cramer
Rainer
R
Camuzeaux
Stephane
S
Tiss
Ali
A
Smith
Celia
C
Burford
Brian
B
Nouretdinov
Ilia
I
Devetyarov
Dmitry
D
Gentry-Maharaj
Aleksandra
A
Ford
Jeremy
J
Luo
Zhiyuan
Z
Gammerman
Alex
A
Menon
Usha
U
Jacobs
Ian
I
D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D001798:Blood Proteins / Q000378:metabolism*; D016022:Case-Control Studies; D003937:Diagnosis, Differential; D020689:Exopeptidases / Q000378:metabolism*; D005260:Female; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000201:enzymology / Q000469:parasitology; D015203:Reproducibility of Results; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods
D014408:Biomarkers, Tumor; D001798:Blood Proteins; D020689:Exopeptidases