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

// Sheila Maria Alvarez-Fernandez 1 , Marco Barbariga 1,5 , Luca Cannizzaro 1,6 , Carlo Vittorio Cannistraci 4 , Laura Hurley 1,7 , Alan Zanardi 1 , Antonio Conti 1 , Francesca Sanvito 2 , Anna Innocenzi 2 , Nicolo Pecorelli 3 , Marco Braga 3 and Massimo Alessio 1 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 Universitat 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.