Abstract
BackgroundThe 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.MethodsThis 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.ResultsSeveral 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.ConclusionsSerum MALDI MS peptide signatures can accurately discriminate patients with BTC from healthy volunteers.
Highlights
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
The aim of this discovery study was to profile peptides in serum collected from patients with BTC, patients with benign biliary disease and healthy volunteers using magnetic C18 bead-based, solid-phase polypeptide extraction followed by MALDI-TOF Mass spectrometry (MS) profiling
Predictive models based on differential peptide peaks generated from a training set were tested on an independent validation set of samples and a subset of the discriminant peptides were identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS)
Summary
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. Further work to identify the serum peptides suggest that they are mostly fragments derived from endogenous proteins of high abundance that may originate from protein breakdown products of the clotting cascade formed ex vivo by cancer-specific exoproteases [13]. The aim of this discovery study was to profile peptides in serum collected from patients with BTC, patients with benign biliary disease and healthy volunteers using magnetic C18 bead-based, solid-phase polypeptide extraction followed by MALDI-TOF MS profiling. Predictive models based on differential peptide peaks generated from a training set were tested on an independent validation set of samples and a subset of the discriminant peptides were identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS)
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