Oncotarget

Clinical Research Papers:

Serological immune response against ADAM10 pro-domain is associated with favourable prognosis in stage III colorectal cancer patients

Sheila María Álvarez-Fernández, Marco Barbariga, Luca Cannizzaro, Carlo Vittorio Cannistraci, Laura Hurley, Alan Zanardi, Antonio Conti, Francesca Sanvito, Anna Innocenzi, Nicolò Pecorelli, Marco Braga and Massimo Alessio _

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Oncotarget. 2016; 7:80059-80076. https://doi.org/10.18632/oncotarget.11181

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Abstract

Sheila María Álvarez-Fernández1, Marco Barbariga1,5, Luca Cannizzaro1,6, Carlo Vittorio Cannistraci4, Laura Hurley1,7, Alan Zanardi1, Antonio Conti1, Francesca Sanvito2, Anna Innocenzi2, Nicolò Pecorelli3, Marco Braga3 and Massimo Alessio1

1 Proteome Biochemistry, IRCCS-San Raffaele Scientific Institute, Milan, Italy

2 Pathology, IRCCS-San Raffaele Scientific Institute, Milan, Italy

3 Department of Surgery, Vita-Salute San Raffaele University, Milan, Italy

4 Biomedical Cybernetics Group, Biotechnology Center (BIOTEC), Center for Molecular and Cellular Bioengineering (CMCB), Technische Universität Dresden, Dresden, Germany

5 Translational Neurology group, Wallenberg Neuroscience Center, BMC, Lund, Sweden

6 Systems Biology Center, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand

7 Wayne State University, School of Medicine, Cancer Biology PhD Program, Detroit, Michigan, USA

Correspondence to:

Massimo Alessio, email:

Keywords: ADAM10 metalloprotease, colorectal carcinoma, immuno-proteomics, autoantibodies, prognosis

Received: April 12, 2016 Accepted: July 10, 2016 Published: August 10, 2016

Abstract

A humoral immune response against aberrant tumor proteins can be elicited in cancer patients, resulting in the production of auto-antibodies (Abs). By serological proteome analysis we identified the surface membrane protein ADAM10, a metalloproteinase that has a role in epithelial-tumor progression and invasion, as a target of the immune response in colorectal cancer (Crc). A screening carried out on the purified protein using testing cohorts of sera (Crc patients n = 57; control subjects n = 39) and validation cohorts of sera (Crc patients n = 49; control subjects n = 52) indicated that anti-ADAM10 auto-Abs were significantly induced in a large group (74%) of colon cancer patients, in particular in patients at stage II and III of the disease. Interestingly, in Crc patients classified as stage III disease, the presence of anti-ADAM10 auto-Abs in the sera was associated with a favourable follow-up with a significant shifting of the recurrence-free survival median time from 23 to 55 months. Even though the ADAM10 protein was expressed in Crc regardless the presence of auto-Abs, the immature/non-functional isoform of ADAM10 was highly expressed in the tumor of anti-ADAM10-positive patients and was the isoform targeted by the auto-Abs. In conclusion, the presence of anti-ADAM10 auto-Abs seems to reflect the increased tumor expression of the immunogenic immature-ADAM10 in a group of Crc patients, and is associated with a favourable prognosis in patients at stage III of the disease.


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