Application of a Serum Protein Signature for Pancreatic Cancer to Separate Cases from Controls in a Pancreatic Surveillance Cohort

Abstract

BACKGROUND: 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. METHODS: Serum samples of 66 individuals with a CDKN2A 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 (n = 4) and individuals with a recent diagnosis of melanoma (n = 4) were also separately considered. RESULTS: Cases had a higher median discriminant score than controls (0.26 vs 0.016; P = .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. CONCLUSIONS: 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.

Dilemmas in the management of screen-detected lesions in patients at high risk for pancreatic cancer

“…Slater et al [8, 9] reported promising results on the use of tumour markers, including micro-RNAs 196a and b, LCN2, and TIMP1. In a small pilot study, the application of proteomics allowed us to differentiate between malignant and benign lesions [10]. However, these findings should be confirmed in larger studies.…”

Novel Metabolomics Serum Biomarkers for Pancreatic Ductal Adenocarcinoma by the Comparison of Pre-, Postoperative and Normal Samples

“…Although these screening modalities are generally able to detect PDAC; none of them have been implemented in daily practice so far due to poor consistency of results [32]. Most of pancreatic cancer metabolomics studies used sample size ranging from 40 to 100 while only a few numbers of studies used more than 500 samples [33][34][35], and insufficient sample size may result in unrepresentative and variable results. Furthermore, there shall be a tendency to recover for effective biomarkers after tumor resection for the post-operative monitoring.…”

Protein Biomarkers for Early Detection of Pancreatic Ductal Adenocarcinoma: Progress and Challenges

“…Large surveillance studies have been conducted on high-risk cohorts with demonstrated survival benefits [ 18 ]. Potjer and colleagues examined performance of a serum-based proteomic panel for early detection in a high-risk cohort undergoing imaging-based surveillance for PDAC [ 46 ]. This study design is one way forward because it incorporates intended use of screening high-risk patients, as well as imaging.…”