Serum AP-endonuclease 1 (sAPE1) as novel biomarker for hepatocellular carcinoma
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Devis Pascut1,*, Caecilia Hapsari Ceriapuri Sukowati1,2,*, Giulia Antoniali2, Giovanna Mangiapane2, Silvia Burra2, Luca Giovanni Mascaretti4, Matteo Rossano Buonocore3, Lory Saveria Crocè3,5,1, Claudio Tiribelli1 and Gianluca Tell2
1Liver Research Center, Fondazione Italiana Fegato, ONLUS, AREA Science Park, Basovizza, Trieste, Italy
2Laboratory of Molecular Biology and DNA Repair, Department of Medicine (DAME), University of Udine, Udine, Italy
3Department of Medical Sciences, University of Trieste, Trieste, Italy
4Transfusion Medicine Department, Azienda Sanitaria Universitaria Integrata di Trieste (ASUITS), Trieste, Italy
5Clinica Patologie Fegato, Azienda Sanitaria Universitaria Integrata di Trieste (ASUITS), Trieste, Italy
*These authors contributed equally to this work
Gianluca Tell, email: email@example.com
Claudio Tiribelli, email: firstname.lastname@example.org
Keywords: APE1; hepatocellular carcinoma; diagnosis; biomarker; DNA repair
Received: November 12, 2018 Accepted: December 27, 2018 Published: January 08, 2019
Late diagnosis for Hepatocellular Carcinoma (HCC) remains one of the leading causes for the high mortality rate. The apurinic/apyrimidinic endonuclease 1 (APE1), an essential member of the base excision DNA repair (BER) pathway, contributes to cell response to oxidative stress and has other non-repair activities. In this study, we evaluate the role of serum APE1 (sAPE1) as a new diagnostic biomarker and we investigate the biological role for extracellular APE1 in HCC. sAPE1 level was quantified in 99 HCC patients, 50 non-HCC cirrhotic and 100 healthy controls. The expression level was significantly high in HCC (75.8 [67.3–87.9] pg/mL) compared to cirrhosis (29.8 [18.3–36.5] pg/mL] and controls (10.8 [7.5–13.2] pg/mL) (p < 0.001). The sAPE1 level corresponded with its protein expression in HCC tissue. sAPE1 had high diagnostic accuracy to differentiate HCC from cirrhotic (AUC = 0.87, sensitivity 88%, specificity 71%, cut-off of 36.3 pg/mL) and healthy subjects (AUC 0.98, sensibility 98% and specificity 83%, cut-off of 19.0 pg/mL). Recombinant APE1, exogenously added to JHH6 cells, significantly promotes IL-6 and IL-8 expression, suggesting a role of sAPE1 as a paracrine pro-inflammatory molecule, which may modulate the inflammatory status in cancer microenvironment. We described herein, for the first time to our knowledge, that sAPE1 might be considered as a promising diagnostic biomarker for HCC.
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