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 exopeptidase activities in serum can generate cancer-predictive peptide fragments from circulating proteins during coagulation

Andreola, F

Blyuss, O

Camuzeaux, S

Chapman, MH

Pereira, SP

Sandanayake, NS

Sinclair, J

Smith, RC

Timms, JF

Webster, GJ

BMC Clinical Pathology

PubMed

Abstract
          
            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.
          </jats:sec

Neomal S Sandanayake

Stephane Camuzeaux

John Sinclair

Oleg Blyuss

Fausto Andreola

Michael H Chapman

George J Webster

Ross C Smith

John F Timms

Stephen P Pereira

Crossref

Identification of potential serum peptide biomarkers of biliary tract cancer using MALDI MS profiling

Springer - Publisher Connector

UCL Discovery

Identification of potential serum peptide biomarkers of biliary tract cancer using MALDI MS profiling.

al: Differential exoprotease activities confer tumor-specific serum peptidome patterns.

al: Preinvasive and invasive ductal pancreatic cancer and its early detection in the mouse. Cancer Cell

Analysis of serum proteomic patterns for early cancer diagnosis: drawing attention to potential problems.

Blumgart LH: Staging, resectability, and outcome in 225 patients with hilar cholangiocarcinoma. Ann Surg

Can mass spectrometric protein profiling meet desired standards of clinical laboratory practice? Clin Chem

Coombes KR: Reproducibility of SELDI-TOF protein patterns in serum: comparing datasets from different experiments. Bioinformatics

DC: Discovery of ovarian cancer biomarkers in serum using NanoLC electrospray ionization TOF and FT-ICR mass spectrometry. Dis Markers

Direct tandem mass spectrometry reveals limitations in protein profiling experiments for plasma biomarker discovery.

DW: Cancer proteomics: serum diagnostics for tumor marker discovery.

et al: Enrichment of low molecular weight fraction of serum for MS analysis of peptides associated with hepatocellular carcinoma. Proteomics

et al: Peptides generated ex vivo from serum proteins by tumor-specific exopeptidases are not useful biomarkers in ovarian cancer. Clin Chem

et al: Use of proteomic patterns in serum to identify ovarian cancer. Lancet

Fleming ID: TNM classification of malignant tumors, fifth edition

Gores GJ: Pathogenesis, diagnosis, and management of cholangiocarcinoma. Gastroenterology

HF: Discovery and validation of new protein biomarkers for urothelial cancer: a prospective analysis. Lancet Oncol

Hoang-Vu C: Biological significance of aminopeptidase N/CD13 in thyroid carcinomas. Cancer Res

Identification and confirmation of increased fibrinopeptide a serum protein levels in gastric cancer sera by magnet bead assisted MALDI-TOF mass spectrometry.

Increasing incidence and mortality of primary intrahepatic cholangiocarcinoma in the United States. Hepatology

Lendeckel U: Ectopeptidases are differentially expressed in hepatocellular carcinomas.

Lessons from controversy: ovarian cancer screening and serum proteomics.

Mass spectrometry as a diagnostic and a cancer biomarker discovery tool: opportunities and potential limitations. Mol Cell Proteomics

Mass spectrometry-based proteomics. Nature

Petricoin E: Clinical proteomics: written in blood. Nature

R: A well-characterised peak identification list of MALDI MS profile peaks for human blood serum. Proteomics

Results of surgical treatment for intrahepatic cholangiocarcinoma and clinicopathological factors influencing survival.

Rocken C: Identification of gastric cancer patients by serum protein profiling.

Role of aminopeptidases in the blood pressure regulation. Biol Pharm Bull

Role of tumour markers, cytogenetics. Ann Oncol

Ruoslahti E: Aminopeptidase N is a receptor for tumor-homing peptides and a target for inhibiting angiogenesis. Cancer Res

SC: Precancerous bile duct pathology in end-stage primary sclerosing cholangitis, with and without cholangiocarcinoma.

Serum peptidome patterns that distinguish metastatic thyroid carcinoma from cancer-free controls are unbiased by gender and age. Mol Cell Proteomics

Serum peptidome profiling revealed platelet factor 4 as a potential discriminating Peptide associated with pancreatic cancer. Clin Cancer Res

Serum proteomics profiling–a young technology begins to mature. Nat Biotechnol

Soluble aminopeptidase N/CD13 in malignant and nonmalignant effusions and intratumoral fluid.

SP: Novel diagnostic and prognostic biomarkers in biliary tract cancer. Expert Opin Med Diagn

Taylor-Robinson SD, Edwards RJ, et al: Elevated levels of neutrophil gelatinase-associated lipocalin in bile from patients with malignant pancreatobiliary disease.

Tempst P: Automated serum peptide profiling. Nat Protoc

Tempst P: Serum peptide profiling by magnetic particle-assisted, automated sample processing and MALDI-TOF mass spectrometry. Anal Chem

The clinical utility of the CA 19–9 tumor-associated antigen.

Thomas HC: Changing international trends in mortality rates for liver, biliary and pancreatic tumours.

Thrombin, thrombomodulin and TAFI in the molecular link between coagulation and fibrinolysis. Thromb Haemost

Todo S: Number of lymph node metastases is a significant prognostic factor in intrahepatic cholangiocarcinoma. World J Surg

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Identification of potential serum peptide biomarkers of biliary tract cancer using MALDI MS profiling.

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Springer - Publisher Connector

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