Lu-177 prostat spesifik membran antijeni (PSMA) ligantlari ile tedavi edilen prostat kanserli hastalarda DNA tamir genlerindeki varyasyonlarin tedavi cevabinin üzerine etkisinin incelenmesi

Lu-177 PSMA has the potential to be a very effective treatment for advanced prostate cancer. The main objectives of this study were to determine whether there is a connection between ERCC2 gene variants, Lu-177 PSMA treatment and the expression levels of miRNA-182 and miRNA-187. This study was conducted on 57 patients. 50 patients were grouped according to whether they received treatment or not, and 7 patients were grouped to examine the changes before and after Lu-177 PSMA treatment. It was found that the expression levels of miRNA-182 (p <0.001) and miRNA-187 were significantly higher in patients who received treatment, including Lu-177 PSMA, than in patients who did not receive any treatment (p = 0.000). The doses that resulted in PSA response as a result of treatment were determined to be 150 mCi and 200 mCi. A significant relationship was found between the post-treatment expression level of miRNA-182 and the change in posttreatment DNA concentration (p = 0.028). The relationship between Lu-177 PSMA treatment and ERCC2 gene variants was investigated in the study groups. It was found that the rs13181 variant was present in both heterozygote mutant and wild type genotypes in patients who received treatment and did not receive treatment. For the rs1799793 variant, it was determined that patients who received treatment had wild-type and homozygous mutant genotypes, while patients who did not receive treatment had homozygous mutant and heterozygous mutant genotypes. When looking at the pre-treatment and post-treatment, it was determined that 50% of the patients with PSA response after treatment had heterozygous mutant for ERCC2 rs13181 variant; 66.66% of the patients who did not have PSA response had wild-type genotype. For ERCC2 rs1799793, it was determined that 100% of those with PSA response were heterozygous mutant, while 50% of those without PSA response had wild-type and 50% had homozygous mutant genotype. In addition, it was found that patients with high post-treatment miRNA-182 levels were more likely to have heterozygous mutant genotype for ERCC2 rs13181 (p = 0.028). In conclusion, it was found that miRNA expressions showed a bimodal feature and that they could vary depending on the dose of treatment, the stage and course of the disease. Monitoring of miRNA-182 expression and analysis of ERCC2 rs13181 and rs1799793 variants can help in the correct planning of personalized Lu-177 PSMA treatment strategies. Key Words: Lu-77 PSMA, Prostate Cancer, miRNA-182, miRNA-187, ERCC2