title: Serological immune response against ADAM10 pro-domain is associated with favourable prognosis in stage III colorectal cancer patients.
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.
authors: Proteome Biochemistry, IRCCS-San Raffaele Scientific Institute, Milan, Italy.
authors: Sheila María
authors: SM
authors: Álvarez-Fernández
authors: Proteome Biochemistry, IRCCS-San Raffaele Scientific Institute, Milan, Italy.|Translational Neurology group, Wallenberg Neuroscience Center, BMC, Lund, Sweden.
authors: Marco
authors: M
authors: Barbariga
authors: Proteome Biochemistry, IRCCS-San Raffaele Scientific Institute, Milan, Italy.|Systems Biology Center, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
authors: Luca
authors: L
authors: Cannizzaro
authors: Biomedical Cybernetics Group, Biotechnology Center (BIOTEC), Center for Molecular and Cellular Bioengineering (CMCB), Technische Universität Dresden, Dresden, Germany.
authors: Carlo Vittorio
authors: CV
authors: Cannistraci
authors: Proteome Biochemistry, IRCCS-San Raffaele Scientific Institute, Milan, Italy.|Wayne State University, School of Medicine, Cancer Biology PhD Program, Detroit, Michigan, USA.
authors: Laura
authors: L
authors: Hurley
authors: Proteome Biochemistry, IRCCS-San Raffaele Scientific Institute, Milan, Italy.
authors: Alan
authors: A
authors: Zanardi
authors: Proteome Biochemistry, IRCCS-San Raffaele Scientific Institute, Milan, Italy.
authors: Antonio
authors: A
authors: Conti
authors: Pathology, IRCCS-San Raffaele Scientific Institute, Milan, Italy.
authors: Francesca
authors: F
authors: Sanvito
authors: Pathology, IRCCS-San Raffaele Scientific Institute, Milan, Italy.
authors: Anna
authors: A
authors: Innocenzi
authors: Department of Surgery, Vita-Salute San Raffaele University, Milan, Italy.
authors: Nicolò
authors: N
authors: Pecorelli
authors: Department of Surgery, Vita-Salute San Raffaele University, Milan, Italy.
authors: Marco
authors: M
authors: Braga
authors: Proteome Biochemistry, IRCCS-San Raffaele Scientific Institute, Milan, Italy.
authors: Massimo
authors: M
authors: Alessio
mesh_terms: D000072197:ADAM10 Protein / Q000737:chemistry / Q000276:immunology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D053829:Amyloid Precursor Protein Secretases / Q000737:chemistry / Q000276:immunology*; D000917:Antibody Formation / Q000502:physiology; D001323:Autoantibodies / Q000097:blood* / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000097:blood; D015179:Colorectal Neoplasms / Q000097:blood* / Q000175:diagnosis* / Q000473:pathology / Q000628:therapy; D005260:Female; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000737:chemistry / Q000276:immunology*; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D000072417:Protein Domains / Q000276:immunology; D011498:Protein Precursors / Q000737:chemistry / Q000276:immunology
chemical_list: D001323:Autoantibodies; D014408:Biomarkers, Tumor; D008565:Membrane Proteins; D011498:Protein Precursors; D053829:Amyloid Precursor Protein Secretases; D000072197:ADAM10 Protein; C491236:ADAM10 protein, human
keywords: ADAM10 metalloprotease; autoantibodies; colorectal carcinoma; immuno-proteomics; prognosis