Circulating Autoantibodies to Phosphorylated α-Enolase are a Hallmark of Pancreatic Cancer.

Tomaino, Barbara; Cappello, Paola; Capello, Michela; Fredolini, Claudia; Sperduti, I; Migliorini, P; Salacone, P; Novarino, A; Giacobino, A; Ciuffreda, L; Alessio, M; Nisticò, P; Scarpa, A; Pederzoli, P; Zhou, W; Petricoin Iii EF,; Liotta, La; Giovarelli, Mirella; Milella, M; Novelli, Francesco; Cappello equally contributo to this work,

doi:10.1021/pr100213b

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.

Titolo:	Circulating Autoantibodies to Phosphorylated α-Enolase are a Hallmark of Pancreatic Cancer.
Autori Riconosciuti:	TOMAINO, BARBARA CAPPELLO, Paola CAPELLO, Michela FREDOLINI, CLAUDIA Sperduti I Migliorini P Salacone P Novarino A Giacobino A Ciuffreda L Alessio M Nisticò P Scarpa A Pederzoli P Zhou W Petricoin Iii EF Liotta LA GIOVARELLI, Mirella Milella M NOVELLI, Francesco Cappello equally contributo to this work mostra contributor esterni nascondi contributor esterni
Autori:	Tomaino B; Cappello P; Capello M; Fredolini C; Sperduti I; Migliorini P; Salacone P; Novarino A; Giacobino A; Ciuffreda L; Alessio M; Nisticò P; Scarpa A; Pederzoli P; Zhou W; Petricoin Iii EF; Liotta LA; Giovarelli M; Milella M; Novelli F. Tomaino and Cappello equally contributo to this work
Data di pubblicazione:	2011
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.
Volume:	10
Fascicolo:	1
Pagina iniziale:	105
Pagina finale:	112
Digital Object Identifier (DOI):	10.1021/pr100213b
URL:	http://pubs.acs.org/doi/abs/10.1021/pr100213b
Parole Chiave:	antibodies; mass spectrometry; pancreatic ductal adenocarcinoma; serological proteome analysis; two-dimensional electrophoresis; tumor associated antigen
Rivista:	JOURNAL OF PROTEOME RESEARCH
Appare nelle tipologie:	03A-Articolo su Rivista

File in questo prodotto:

File	Descrizione	Tipologia	Licenza
Tomaino_JPR_2010.pdf		POSTPRINT (VERSIONE FINALE DELL’AUTORE)	Accesso aperto	Open Access Visualizza/Apri
Tomaino B JProteomRes 2011.pdf		PDF EDITORIALE		Utenti riconosciuti Richiedi una copia

Utilizza questo identificativo per citare o creare un link a questo documento:
http://hdl.handle.net/2318/82073

Citazioni

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

CINECA IRIS Institutional Research Information System

File in questo prodotto: