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, Massimo Alessio

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)80059-80076
Number of pages18
JournalOncotarget
Volume7
Issue number48
DOIs
Publication statusPublished - 2016

Fingerprint

Colorectal Neoplasms
Antibodies
Neoplasms
Protein Isoforms
Membrane Proteins
Serum
Metalloproteases
Proteome
Humoral Immunity
Colonic Neoplasms
Antibody Formation
Proteins
Recurrence
Survival

Keywords

  • ADAM10 metalloprotease
  • Autoantibodies
  • Colorectal carcinoma
  • Immuno-proteomics
  • Prognosis

ASJC Scopus subject areas

  • Oncology

Cite this

Álvarez-Fernández, S. M., Barbariga, M., Cannizzaro, L., Cannistraci, C. V., Hurley, L., Zanardi, A., ... Alessio, M. (2016). Serological immune response against ADAM10 pro-domain is associated with favourable prognosis in stage III colorectal cancer patients. Oncotarget, 7(48), 80059-80076. https://doi.org/10.18632/oncotarget.11181

Serological immune response against ADAM10 pro-domain is associated with favourable prognosis in stage III colorectal cancer patients. / Álvarez-Fernández, Sheila María; Barbariga, Marco; Cannizzaro, Luca; Cannistraci, Carlo Vittorio; Hurley, Laura; Zanardi, Alan; Conti, Antonio; Sanvito, Francesca; Innocenzi, Anna; Pecorelli, Nicolò; Braga, Marco; Alessio, Massimo.

In: Oncotarget, Vol. 7, No. 48, 2016, p. 80059-80076.

Research output: Contribution to journalArticle

Álvarez-Fernández, SM, Barbariga, M, Cannizzaro, L, Cannistraci, CV, Hurley, L, Zanardi, A, Conti, A, Sanvito, F, Innocenzi, A, Pecorelli, N, Braga, M & Alessio, M 2016, 'Serological immune response against ADAM10 pro-domain is associated with favourable prognosis in stage III colorectal cancer patients', Oncotarget, vol. 7, no. 48, pp. 80059-80076. https://doi.org/10.18632/oncotarget.11181
Álvarez-Fernández, Sheila María ; Barbariga, Marco ; Cannizzaro, Luca ; Cannistraci, Carlo Vittorio ; Hurley, Laura ; Zanardi, Alan ; Conti, Antonio ; Sanvito, Francesca ; Innocenzi, Anna ; Pecorelli, Nicolò ; Braga, Marco ; Alessio, Massimo. / Serological immune response against ADAM10 pro-domain is associated with favourable prognosis in stage III colorectal cancer patients. In: Oncotarget. 2016 ; Vol. 7, No. 48. pp. 80059-80076.
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AB - 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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