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

Keywords

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

ASJC Scopus subject areas

  • Oncology

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  • Cite this

    Álvarez-Fernández, S. M., Barbariga, M., Cannizzaro, L., Cannistraci, C. V., 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, 7(48), 80059-80076. https://doi.org/10.18632/oncotarget.11181