TY - JOUR
T1 - Circulating autoantibodies to phosphorylated α-enolase are a hallmark of pancreatic cancer
AU - Tomaino, Barbara
AU - Cappello, Paola
AU - Capello, Michela
AU - Fredolini, Claudia
AU - Sperduti, Isabella
AU - Migliorini, Paola
AU - Salacone, Paola
AU - Novarino, Anna
AU - Giacobino, Alice
AU - Ciuffreda, Libero
AU - Alessio, Massimo
AU - Nisticò, Paola
AU - Scarpa, Aldo
AU - Pederzoli, Paolo
AU - Zhou, Weidong
AU - Petricoin, Emanuel F.
AU - Liotta, Lance A.
AU - Giovarelli, Mirella
AU - Milella, Michele
AU - Novelli, Francesco
PY - 2011/1/7
Y1 - 2011/1/7
N2 - Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis and no diagnostic markers have, as of yet, been defined. In PDAC patients, R-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 thatENOAphosphorylation is associated with PDAC and induces specific autoantibody production in PDAC patients that may have diagnostic value.
AB - Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis and no diagnostic markers have, as of yet, been defined. In PDAC patients, R-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 thatENOAphosphorylation is associated with PDAC and induces specific autoantibody production in PDAC patients that may have diagnostic value.
KW - Antibodies
KW - Mass spectrometry
KW - Pancreatic ductal adenocarcinoma
KW - Serological proteome analysis
KW - Tumor associated antigen
KW - Two-dimensional electrophoresis
UR - http://www.scopus.com/inward/record.url?scp=79951526292&partnerID=8YFLogxK
U2 - 10.1021/pr100213b
DO - 10.1021/pr100213b
M3 - Article
C2 - 20455595
AN - SCOPUS:79951526292
SN - 1535-3893
VL - 10
SP - 105
EP - 112
JO - Journal of Proteome Research
JF - Journal of Proteome Research
IS - 1
ER -