Identification of potential serum peptide biomarkers of biliary tract cancer using MALDI MS profiling.
BACKGROUND
The aim of this discovery study was the identification of peptide serum biomarkers for detecting biliary tract cancer (BTC) using samples from healthy volunteers and benign cases of biliary disease as control groups. This work was based on the hypothesis that cancer-specific exopeptidases exist and that their activities in serum can generate cancer-predictive peptide fragments from circulating proteins during coagulation.


METHODS
This case control study used a semi-automated platform incorporating polypeptide extraction linked to matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS) to profile 92 patient serum samples. Predictive models were generated to test a validation serum set from BTC cases and healthy volunteers.


RESULTS
Several peptide peaks were found that could significantly differentiate BTC patients from healthy controls and benign biliary disease. A predictive model resulted in a sensitivity of 100% and a specificity of 93.8% in detecting BTC in the validation set, whilst another model gave a sensitivity of 79.5% and a specificity of 83.9% in discriminating BTC from benign biliary disease samples in the training set. Discriminatory peaks were identified by tandem MS as fragments of abundant clotting proteins.


CONCLUSIONS
Serum MALDI MS peptide signatures can accurately discriminate patients with BTC from healthy volunteers.
UCL Institute for Liver and Digestive Health, Royal Free Hospital Campus, University College London, London, UK.|Cancer Proteomics Laboratory, EGA Institute for Women's Health, University College London, London, UK.|Kolling Institute, University of Sydney, St Leonards, Australia.
Neomal S
NS
Sandanayake
Cancer Proteomics Laboratory, EGA Institute for Women's Health, University College London, London, UK.
Stephane
S
Camuzeaux
Cancer Proteomics Laboratory, EGA Institute for Women's Health, University College London, London, UK.
John
J
Sinclair
Cancer Proteomics Laboratory, EGA Institute for Women's Health, University College London, London, UK.
Oleg
O
Blyuss
UCL Institute for Liver and Digestive Health, Royal Free Hospital Campus, University College London, London, UK.
Fausto
F
Andreola
UCL Institute for Liver and Digestive Health, Royal Free Hospital Campus, University College London, London, UK.|Department of Gastroenterology, University College Hospitals NHS Foundation Trust, London, UK.
Michael H
MH
Chapman
UCL Institute for Liver and Digestive Health, Royal Free Hospital Campus, University College London, London, UK.|Department of Gastroenterology, University College Hospitals NHS Foundation Trust, London, UK.
George J
GJ
Webster
Kolling Institute, University of Sydney, St Leonards, Australia.
Ross C
RC
Smith
Cancer Proteomics Laboratory, EGA Institute for Women's Health, University College London, London, UK.
John F
JF
Timms
UCL Institute for Liver and Digestive Health, Royal Free Hospital Campus, University College London, London, UK.|Department of Gastroenterology, University College Hospitals NHS Foundation Trust, London, UK.
Stephen P
SP
Pereira