A Quantitative Global Proteomics Approach Identifies Candidate Urinary Biomarkers That Correlate With Intraductal Papillary Mucinous Neoplasm Dysplasia

Katelyn F. Flick, Michele Yip-Schneider, Christopher M. Sublette, Rachel E. Simpson, Cameron L. Colgate, Huangbing Wu, Mazhar Soufi, John DeWitt, Amber L. Mosley, Eugene P. Ceppa, Jianjun Zhang, C. Max Schmidt

Research output: Contribution to journalArticle

Abstract

OBJECTIVES: A proteomic discovery study was performed to determine if urine possesses a unique biosignature that could form the basis for a noninvasive test able to predict intraductal papillary mucinous neoplasm (IPMN) dysplasia. METHODS: Urine was collected from patients undergoing surgery for IPMN (72 low/moderate, 27 high-grade/invasive). Quantitative mass spectrometry-based proteomics was performed. Proteins of interest were identified by differential expression analysis followed by principal component analysis. RESULTS: Proteomics identified greater than 4800 urinary proteins. Low/moderate and high-grade/invasive IPMN were distinguished by 188 proteins (P < 0.05). Following principal component analysis and heatmap visualization, vitamin D binding protein (DBP), apolipoprotein A1 (APOA1), and alpha-1 antitrypsin (A1AT) were selected. The proteomic abundance of DBP (median [interquartile range]) was significantly higher for high-grade/invasive than for low/moderate IPMN (219,735 [128,882-269,943] vs. 112,295 [77,905-180,773] normalized reporter ion intensity units; P = 0.001). Similarly, APOA1 was more abundant in the high-grade/invasive than low/moderate groups (235,420 [144,933-371,247] vs 150,095 [103,419-236,591]; P = 0.0007) as was A1AT (567,514 [358,544-774,801] vs 358,393 [260,850-477,882]; P = 0.0006). CONCLUSIONS: Urinary DBP, APOA1, and A1AT represent potential biomarker candidates that may provide a noninvasive means of predicting IPMN dysplastic grade.

Original languageEnglish (US)
Pages (from-to)1044-1051
Number of pages8
JournalPancreas
Volume49
Issue number8
DOIs
StatePublished - Sep 1 2020

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Hepatology
  • Endocrinology

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