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EnglishPancreatic 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: | |
| 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 |
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| File | Descrizione | Tipologia | Licenza | |
|---|---|---|---|---|
| Tomaino_JPR_2010.pdf | 1 Ver. finale autore | Accesso aperto | Open Access Visualizza/Apri | |
| Tomaino B JProteomRes 2011.pdf | 2 PDF Editoriale | Utenti riconosciuti Richiedi una copia |
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