Autoantibodies to Ezrin are an early sign of pancreatic cancer in humans and in genetically engineered mouse models

Michela Capello, Paola Cappello, Federica Caterina Linty, Roberto Chiarle, Isabella Sperduti, Anna Novarino, Paola Salacone, Giorgia Mandili, Alessio Naccarati, Carlotta Sacerdote, Stefania Beghelli, Samantha Bersani, Stefano Barbi, Claudio Bassi, Aldo Scarpa, Paola Nisticò, Mirella Giovarelli, Paolo Vineis, Michele Milella, Francesco Novelli

Research output: Contribution to journalArticle

Abstract

Background: Pancreatic Ductal Adenocarcinoma (PDAC) is a highly aggressive malignancy with only a 5% 5-year survival rate. Reliable biomarkers for early detection are still lacking. The goals of this study were (a) to identify early humoral responses in genetically engineered mice (GEM) spontaneously developing PDAC; and (b) to test their diagnostic/predictive value in newly diagnosed PDAC patients and in prediagnostic sera. Methods and results. The serum reactivity of GEM from inception to invasive cancer, and in resectable or advanced human PDAC was tested by two-dimensional electrophoresis Western blot against proteins from murine and human PDAC cell lines, respectively. A common mouse-to-human autoantibody signature, directed against six antigens identified by MALDI-TOF mass spectrometry, was determined. Of the six antigens, Ezrin displayed the highest frequency of autoantibodies in GEM with early disease and in PDAC patients with resectable disease. The diagnostic value of Ezrin-autoantibodies to discriminate PDAC from controls was further shown by ELISA and ROC analyses (P <0.0001). This observation was confirmed in prediagnostic sera from the EPIC prospective study in patients who eventually developed PDAC (with a mean time lag of 61.2 months between blood drawing and PDAC diagnosis). A combination of Ezrin-autoantibodies with CA19.9 serum levels and phosphorylated Enolase autoantibodies showed an overall diagnostic accuracy of 0.96 ± 0.02. Conclusions: Autoantibodies against Ezrin are induced early in PDAC and their combination with other serological markers may provide a predictive and diagnostic signature.

Original languageEnglish
Article number67
JournalJournal of Hematology and Oncology
Volume6
Issue number1
DOIs
Publication statusPublished - 2013

Keywords

  • Early diagnosis
  • Ezrin
  • Genetically engineered mouse model
  • Pancreatic ductal adenocarcinoma
  • Tumor antigen

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research
  • Molecular Biology

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    Capello, M., Cappello, P., Linty, F. C., Chiarle, R., Sperduti, I., Novarino, A., Salacone, P., Mandili, G., Naccarati, A., Sacerdote, C., Beghelli, S., Bersani, S., Barbi, S., Bassi, C., Scarpa, A., Nisticò, P., Giovarelli, M., Vineis, P., Milella, M., & Novelli, F. (2013). Autoantibodies to Ezrin are an early sign of pancreatic cancer in humans and in genetically engineered mouse models. Journal of Hematology and Oncology, 6(1), [67]. https://doi.org/10.1186/1756-8722-6-67