RESUMO
The thyroid hormone plays a vital role in the development and maturation of the nervous system not only during prenatal and perinatal age but also in adults. "Peripheral marker hypothesis" revealed that gene expression changes in some regions of the brain are reflected into the peripheral blood lymphocytes. The objective of the study was to investigate changes in the gene expression profile of neuropeptides and their receptors in patients with different forms of thyroid pathology. One hundred fifty-three patients with thyroid pathology were enrolled in the study. They were divided into three groups: group 1 included 16 patients with postoperative hypothyroidism, group 2 included 65 patients with hypothyroidism resulting from autoimmune thyroiditis (AIT), and group 3 included 72 patients with AIT and elevated levels of anti-thyroglobulin (anti-Tg) and anti-thyroid peroxidase (anti-TPO) antibodies in the serum. We used a pathway-specific polymerase chain reaction (PCR) array (RT2 Profiler™ PCR Array Human Neurotrophins & Receptors, QIAGEN, Germany) to identify and verify neuropeptides and receptors pathway-focused gene expression in 12 individuals that were randomly selected from each group using real-time PCR. Our research identified that patients with postoperative hypothyroidism had a considerably increased expression of NPY1R, NTSR1, and NPY4R. The patients with hypothyroidism caused by autoimmune thyroiditis had considerably lower expression of NTSR1, while the expression of NPY1R increased. The mRNA levels of NPY2R and PNOC increased in the patients with elevated levels of autoantibodies anti-Tg and anti-TPO in the serum, and mRNA levels of NPY1R and NTSR1 decreased in this group of patients.
Assuntos
Neuropeptídeos/sangue , Neuropeptídeos/genética , Receptores de Neuropeptídeos/sangue , Receptores de Neuropeptídeos/genética , Glândula Tireoide/patologia , Transcrição Gênica , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Alemanha , Humanos , Hipotireoidismo/sangue , Hipotireoidismo/genética , Pessoa de Meia-Idade , Neuropeptídeos/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores de Neuropeptídeos/metabolismo , Tireoidite Autoimune/sangue , Tireoidite Autoimune/genéticaRESUMO
Recognition of molecular diversity in disease is required for the development of targeted therapies. We have developed a screening method based on phage display to select peptides recognized by the repertoire of circulating tumor-associated antibodies. Here we isolated peptides recognized by antibodies purified from the serum of prostate cancer patients. We identified a consensus motif, NX(S/T)DK(S/T), that bound selectively to circulating antibodies from cancer patients over control antibodies from blood donors. We validated this motif by showing that positive serum reactivity to the peptide was specifically linked to disease progression and to shorter survival in a large patient population. Moreover, we identified the corresponding protein eliciting the immune response. Finally, we showed a strong and specific positive correlation between serum reactivity to the tumor antigen, development of metastatic androgen-independent disease, and shorter overall survival. Exploiting the differential humoral response to cancer through such an approach may identify molecular markers and targets for diagnostic and therapeutic intervention.