Proteome heterogeneity and malignancy detection in pancreatic cyst fluids

Dear Editor: Pancreatic cyst neoplasms (PCNs), such as intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms (MCNs), represent one of the main dysplastic precursor lesions that could give rise to invasive pancreatic carcinoma.1,2 While guidelines have been suggested to assist in the diagnosis and management of PCNs, including resection and surveillance recommendations,3,4 clinical management of cyst lesions remains imprecise due to difficulties in accurately detecting high-risk or invasive lesions and uncertainty in predicting the malignant potential of these lesions. Current diagnostic evaluations of PCNs, including cyst size and morphology, worrisome features, main pancreatic duct dilation, CA19-9, cytology, and cyst fluid analysis (CEA, amylase), can discriminate between mucinous and non-mucinous cysts and classify cyst types with some certainty, but they do not provide a definite clinical diagnosis of PCNs with high-risk or invasive lesions.5,6 A biomarker test that can effectively assist PCN risk stratification and treatment decision-making would be clinically valuable. Functional analysis indicated that many cyst fluid proteins were involved in cell-cell adhesion, proteolysis and innate immune response, more than 30% of the proteins were related to signaling, and ∼67% and ∼53% were subject to changes due to polymorphism or alternative splicing, respectively (Figure S1). Using a selected group of pancreatic cancer-associated proteins with an elevated concentration in Carcinoma/HGD (p < 0.05) and pancreatic enzymes, a principal component analysis was able to clearly seperate the Carcinoma/HGD cases from Benign/LGD cases (Figure 3A).