文摘
m>BACKGROUND:m> Pancreatic cancer (PC) surveillance is currently offered to individuals with a genetic predisposition to PC, but routinely used radiological screening modalities are not entirely reliable in detecting early-stage PC or its precursor lesions. We recently identified a discriminating PC biomarker signature in a sporadic patient cohort. In this study, we investigated if protein profiling can accurately distinguish PC from non-PC in a pancreatic surveillance cohort of genetically predisposed individuals. m>METHODS:m> Serum samples of 66 individuals with a m>CDKN2Am> germline mutation who participated in the pancreatic surveillance program (5 cases, 61 controls) were obtained following a standardized protocol. After sample clean-up, peptide and protein profiles were obtained on an ultrahigh-resolution matrix-assisted laser desorption/ionization–Fourier transform ion cyclotron resonance mass spectrometry platform. A discriminant score for each sample was calculated with a previously designed prediction rule, and the median discriminant scores of cases and controls were compared. Individuals with precursor lesions of PC (m>nm> = 4) and individuals with a recent diagnosis of melanoma (m>nm> = 4) were also separately considered. m>RESULTS:m> Cases had a higher median discriminant score than controls (0.26 vs 0.016; m>Pm> = .001). The only individual with pathologically confirmed precursor lesions of PC could also be clearly distinguished from controls, and having a (recent) medical history of melanoma did not influence the protein signatures. m>CONCLUSIONS:m> Peptide and protein signatures are able to accurately distinguish PC cases from controls in a pancreatic surveillance setting. Mass spectrometry–based protein profiling therefore seems to be a promising candidate for implementation in the pancreatic surveillance program as an additional screening modality.
