Identification of Cystic Precursors to Pancreatic Cancer Using Targeted Mass Spectrometry


Key Points A peptide panel from MUC5AC and MUC2 distinguished premalignant/malignant lesions from benign lesions with an accuracy of 97%.

A panel consisting of MUC5AC proteins and PSCA identified high-grade dysplasia/cancer with an accuracy of 96%.

In a study reported in the Journal of Clinical Oncology, Jabbar et al found that mass spectroscopy proteomic analysis of the pancreatic cyst fluid biomarkers mucin-5AC (MUC5AC), mucin-2 (MUC2), and prostate stem cell antigen (PSCA) identified cystic pancreatic cancers and precursor lesions with high accuracy.

Study Details

In the study, biomarker candidates for malignant potential and high-grade dysplasia/cancer were identified via an explorative proteomic approach using cyst fluid samples from endoscopic ultrasound-guided aspiration in an initial cohort of 24 patients. Quantitative analysis using 30 heavy-labeled peptides from the biomarkers and parallel reaction monitoring mass spectrometry was tested in a training cohort of 80 patients and then prospectively evaluated in a validation cohort of 68 patients.

Biomarker Performance

A peptide panel from MUC5AC and MUC2 constituted the set of markers that optimally distinguished premalignant/malignant lesions from benign lesions. In the validation cohort, accuracy of the panel was 97%, compared with 61% using cyst fluid carcinoembryonic antigen (P < .001) and 84% using cytology (P = .02). A panel consisting of MUC5AC proteins and PSCA identified high-grade dysplasia/cancer with an accuracy of 96% and detected 95% of malignant/severely dysplastic lesions, compared with 35% for carcinoembryonic antigen ( P< .001) and 50% for cytology (P = .003).

The investigators concluded: “Targeted mass spectrometry analysis of just three cyst fluid biomarkers provides highly accurate identification and assessment of cystic precursors to pancreatic adenocarcinoma. Additional studies should determine whether the method can facilitate timely cancer diagnosis, successful intervention, and prevention.”

The study was supported by the Swedish Cancer Foundation, BioCARE research foundation, Swedish Research Council, Knut and Alice Wallenberg Foundation, and others.

Gunnar C. Hansson, MD, PhD, of the Department of Medical Biochemistry, University of Gothenburg, is the corresponding author of the Journal of Clinical Oncology article.