Análise molecular da expressão dos genes KLK2 e KLK3 e suas implicações no diagnóstico do câncer de próstata

Abstract

The prostate câncer (PCa) has become one of the most important and common diseases in elderiy men. It is the second diagnosed câncer in Brazil and in USA after the melanorna câncer. The tracing of prostatic anomalies is donc by physical examination (digital exam), laboratory analysis ofthe prostate specific antigen (PSA) and the trans-rectum uitrasound, followed by confirmatory biopsies. The molecular markers utilization in clinicai procedures may improve the diagnosis through an early detection of prostate câncer, increasing the chance of cure. This investigation aimed analysing gene expression leveis of KLK2 and KLK3 (PSA) in both peripheral blood and prostate biopsies of patients with prostate câncer and benign prostatic hyperplasia (BPH). A semiquantitative multiplex RTPCR was used to estimate transcriptional leveis of KLK2 and KLK3 genes in prostate tissues, for which it has been deinonstrated that only KLK2 was able to discriminate PCa from BPH. Clinicai applications of this result may have important implications to the diagnosties. A 0.6 boderline limit (greater than 60% of the constitutive gene expression levei) in biopsies had an odds ratio of 15, favorable to the tumor development. The borderline limit obtained for one or two biopsies ofthe same patient presented a risk factor of 7 and 45, respectively. The qualitative analysis to the KLK2 in the peripheral blood by semi-nested RT-PCR (presence or absence) has allowed discrimination between PCa and BPH patients, with a calculated risk 6 times greater for the tumor presence. This work of KLK2 expression leveis in prostate tissues had an estimated accuracy of 81%, sensisitivity of 86%, specificity of 71.4%, predictive positive value of 86%, and predictive negative value of 71%. In the peripheral blood the precision was 67%, sensitivity of 59%, specificity of 82%, predictive positive value of 87% and predictive negative value of 50%. The combined analysis of the KLK2 in blood and biopsies has permitted a new proposal for clinicai examination routine. The molecular diagnostic had a precision of 92%, considering the detection in blood and in biopsies. The association of serum PSA, histological analyses and molecular markers may provide a more accurate diagnostic.