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

Álvarez-Fernández, Sheila María; Barbariga, Marco LU ; Cannizzaro, Luca; Cannistraci, Carlo Vittorio; Hurley, Laura; Zanardi, Alan; Conti, Antonio; Sanvito, Francesca; Innocenzi, Anna and Pecorelli, Nicolò, et al. (2016) In Oncotarget 7(48). p.80059-80076
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... (More)

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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Contribution to journal
publication status
published
subject
keywords
ADAM10 metalloprotease, Autoantibodies, Colorectal carcinoma, Immuno-proteomics, Prognosis
in
Oncotarget
volume
7
issue
48
pages
18 pages
publisher
Impact Journals, LLC
external identifiers
  • scopus:84999040240
ISSN
1949-2553
DOI
10.18632/oncotarget.11181
language
English
LU publication?
yes
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55b69338-ac54-49c7-9b28-15dc5aecfb12
date added to LUP
2016-12-29 12:24:32
date last changed
2017-11-14 09:51:15
@article{55b69338-ac54-49c7-9b28-15dc5aecfb12,
  abstract     = {<p>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.</p>},
  author       = {Álvarez-Fernández, Sheila María and Barbariga, Marco and Cannizzaro, Luca and Cannistraci, Carlo Vittorio and Hurley, Laura and Zanardi, Alan and Conti, Antonio and Sanvito, Francesca and Innocenzi, Anna and Pecorelli, Nicolò and Braga, Marco and Alessio, Massimo},
  issn         = {1949-2553},
  keyword      = {ADAM10 metalloprotease,Autoantibodies,Colorectal carcinoma,Immuno-proteomics,Prognosis},
  language     = {eng},
  number       = {48},
  pages        = {80059--80076},
  publisher    = {Impact Journals, LLC},
  series       = {Oncotarget},
  title        = {Serological immune response against ADAM10 pro-domain is associated with favourable prognosis in stage III colorectal cancer patients},
  url          = {http://dx.doi.org/10.18632/oncotarget.11181},
  volume       = {7},
  year         = {2016},
}