Proteomic Assessment of Markers for Malignancy in the Mucus of Intraductal Papillary Mucinous Neoplasms of the Pancreas

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Abstract

Objectives

Intraductal papillary mucinous neoplasms (IPMN) of the pancreas evolve from dysplasia to invasive adenocarcinoma. The aims of this study were to look for candidate protein profiles in IPMN mucus according to histological grade, using a differential proteomic technique, and to highlight protein peaks associated with malignant transformation.

Methods

Forty-three mucus samples obtained from surgically resected IPMN and categorized as benign (low/moderate dysplasia) or malignant (severe dysplasia/invasive adenocarcinoma) in 21 and 22 patients, respectively. A surface-enhanced laser desorption ionization time-of-flight mass spectrometry was used to determine candidate protein expression profiles. Protein peaks that significantly differed between benign/malignant IPMN (area under curve > 0.88; P < 10−4; high intensity) were identified using adapted software.

Results

Among 952 protein peaks, 31 were differentially expressed in benign/malignant IPMN (P < 0.001). Among them, 5 candidate proteins of interest (mass-to-charge ratio [m/z]: 5217, 6326, 6719, 10,453, and 10,849 d) were selected by their high diagnostic accuracy and ability to distinguish between malignant and benign tumors. No correlation was found between peak profiles and duct involvement.

Conclusions

Carcinogenic process in IPMN is associated with changes in mucus proteome with characteristic peaks that could be potential candidate biomarkers of malignancy.

Abbreviations

IPMN - intraductal papillary mucinous neoplasm, EPC - extrapancreatic cancer, MRI - magnetic resonance imaging, ERCP - endoscopic retrograde cholangiopancreatography

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