RESUMO
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.
Assuntos
Proteína ADAM10/imunologia , Secretases da Proteína Precursora do Amiloide/imunologia , Autoanticorpos/sangue , Neoplasias Colorretais/sangue , Neoplasias Colorretais/diagnóstico , Proteínas de Membrana/imunologia , Proteína ADAM10/química , Adulto , Idoso , Idoso de 80 Anos ou mais , Secretases da Proteína Precursora do Amiloide/química , Formação de Anticorpos/fisiologia , Autoanticorpos/metabolismo , Biomarcadores Tumorais/sangue , Neoplasias Colorretais/patologia , Neoplasias Colorretais/terapia , Feminino , Humanos , Masculino , Proteínas de Membrana/química , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Domínios Proteicos/imunologia , Precursores de Proteínas/química , Precursores de Proteínas/imunologiaRESUMO
Natural autoantibodies raised by humoral immune response to cancer can be exploited to identify potential tumor-associated antigens (TAAs), and might constitute new putative prognostic and/or diagnostic biomarkers. Here we describe how sera from tumor patients can be used to identify TAAs by screening antibody immunoreactivity against the cancer proteome resolved by two-dimensional gel electrophoresis.
