title: 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.affiliation: Center for Experimental Research and Medical Studies (CeRMS), San Giovanni Battista Hospital, Turin, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Tomaino
authors.forename: Paola
authors.initials: P
authors.lastname: Cappello
authors.forename: Michela
authors.initials: M
authors.lastname: Capello
authors.forename: Claudia
authors.initials: C
authors.lastname: Fredolini
authors.forename: Isabella
authors.initials: I
authors.lastname: Sperduti
authors.forename: Paola
authors.initials: P
authors.lastname: Migliorini
authors.forename: Paola
authors.initials: P
authors.lastname: Salacone
authors.forename: Anna
authors.initials: A
authors.lastname: Novarino
authors.forename: Alice
authors.initials: A
authors.lastname: Giacobino
authors.forename: Libero
authors.initials: L
authors.lastname: Ciuffreda
authors.forename: Massimo
authors.initials: M
authors.lastname: Alessio
authors.forename: Paola
authors.initials: P
authors.lastname: Nisticò
authors.forename: Aldo
authors.initials: A
authors.lastname: Scarpa
authors.forename: Paolo
authors.initials: P
authors.lastname: Pederzoli
authors.forename: Weidong
authors.initials: W
authors.lastname: Zhou
authors.forename: Emanuel F
authors.initials: EF
authors.lastname: Petricoin Iii
authors.forename: Lance A
authors.initials: LA
authors.lastname: Liotta
authors.forename: Mirella
authors.initials: M
authors.lastname: Giovarelli
authors.forename: Michele
authors.initials: M
authors.lastname: Milella
authors.forename: Francesco
authors.initials: F
authors.lastname: Novelli
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000737:chemistry / Q000378:metabolism; D001323:Autoantibodies / Q000097:blood* / Q000378:metabolism; D015153:Blotting, Western; D021441:Carcinoma, Pancreatic Ductal / Q000097:blood / Q000175:diagnosis*; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000097:blood / Q000175:diagnosis*; D010751:Phosphopyruvate Hydratase / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation; D011379:Prognosis; D016016:Proportional Hazards Models; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism; D012372:ROC Curve
chemical_list: D000951:Antigens, Neoplasm; D001323:Autoantibodies; D020033:Protein Isoforms; D010751:Phosphopyruvate Hydratase