Seleção e caracterização de peptídeos miméticos a proteínas tumorais no estadiamento clínico-patológico do câncer de próstata

Abstract

Prostate cancer is the second cause of deaths by tumor in men, surpassed only to lung cancer. Currently, PSA (prostate-specific antigen) is clinical test of choice for PCa detection and treatment. However, the limitations of the PSA test such as large number of false positive results and unnecessary biopsies indicate the need for other means of screening for this neoplasm. Identification of new genes or antigens specific for prostate cancer, study of molecular recognition, and innovation in cancer diagnostics, can provide the development of new biomarkers, specific therapies, as well as provide faster diagnostic to assist doctors. This work was performed a screening method based on phage display to select peptides recognized by the repertoire of circulating tumor-associated antibodies and standardized the coupling of the phages to microspheres for the development of a diagnostic platform to obtain or biomarkers in the discovery of new etiologies for the tumor. We isolated peptides recognized by purified antibodies from serum of prostate cancer patients. For selection of peptides was performed a subtractive bioppaning, followed by positive selection using a library of peptides Ph.D.-C7C expressed on the surface of filamentous phage M13. The DNA from selected phages was sequenced, translated, and the various clones were subjected to ELISA assays and bioinformatics. Analysis of the sequences of selected clones had a common reason FPWL, which were linked with tumor staging pT1 and pT2, and specifically to cancer associated with prostatic intraepithelial neoplasia. One clone with a different sequence recognized the tumor staging pT4 and none for pT3. Procedure for the coupling of the phages used in the microspheres is different in different pH buffers and found that the combination was effective, except for the sodium phosphate buffer 1.2 M pH 10.2. Exploiting the differential humoral response to cancer through may identify molecular markers and targets for diagnostic and therapeutic intervention. Furthermore, the development of a new diagnostic methods can provide results faster and with less cost.