Circulating autoantibodies to phosphorylated α-enolase are a hallmark of pancreatic cancer.

Abstract

Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis and no diagnostic markers have, as of yet, been defined. In PDAC patients, α-enolase (ENOA) is up-regulated and elicits the production of autoantibodies. Here, we analyzed the autoantibody response to post-translational modifications of ENOA in PDAC patients. ENOA isolated from PDAC tissues and cell lines was characterized by two-dimensional electrophoresis (2-DE) Western blot (WB), revealing the expression of six different isoforms (named ENOA1,2,3,4,5,6) whereas only 4 isoforms (ENOA3,4,5,6) were detectable in normal tissues. As assessed by 2-DE WB, 62% of PDAC patients produced autoantibodies to the two more acidic isoforms (ENOA1,2) as opposed to only 4% of controls. Mass spectrometry showed that ENOA1,2 isoforms were phosphorylated on serine 419. ROC analysis demonstrated that autoantibodies to ENOA1,2 usefully complement the diagnostic performance of serum CA19.9 levels, achieving approximately 95% diagnostic accuracy in both advanced and resectable PDAC. Moreover, the presence of autoantibodies against ENOA1,2 correlated with a significantly better clinical outcome in advanced patients treated with standard chemotherapy. In conclusion, our results demonstrate that ENOA phosphorylation is associated with PDAC and induces specific autoantibody production in PDAC patients that may have diagnostic value.

• Authors: Barbara Tomaino, Paola Cappello, Michela Capello, Claudia Fredolini, Isabella Sperduti, Paola Migliorini, Paola Salacone, Anna Novarino, Alice Giacobino, Libero Ciuffreda, Massimo Alessio, Paola Nisticò, Aldo Scarpa, Paolo Pederzoli, Weidong Zhou, Emanuel F Petricoin Iii, Lance A Liotta, Mirella Giovarelli, Michele Milella, Francesco Novelli
• Journal: Journal of proteome research (J Proteome Res) Vol. 10 Issue 1 Pg. 105-12 (Jan 07 2011) ISSN: 1535-3907 [Electronic] United States
• PMID: 20455595 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Neoplasm
• Autoantibodies
• Protein Isoforms
• Phosphopyruvate Hydratase

Topics

• Adult
• Aged
• Aged, 80 and over
• Antigens, Neoplasm (chemistry, metabolism)
• Autoantibodies (blood, metabolism)
• Blotting, Western
• Carcinoma, Pancreatic Ductal (blood, diagnosis)
• Electrophoresis, Gel, Two-Dimensional
• Female
• Humans
• Male
• Middle Aged
• Pancreatic Neoplasms (blood, diagnosis)
• Phosphopyruvate Hydratase (chemistry, metabolism)
• Phosphorylation
• Prognosis
• Proportional Hazards Models
• Protein Isoforms (chemistry, metabolism)
• ROC Curve