Savremeni pristupi u istraživanju molekularne osnove karcinoma prostate

Abstract

U ovom radu preglednog tipa prikazano je desetogodišnje iskustvo istraživačkog tima PRO- STATSERBIA koji za temu svog istraživanja ima molekularnu osnovu karcinoma prostate (KP). Centar za humanu molekularnu genetiku Biološkog fakulteta Univerziteta u Beogradu poseduje kolekciju uzoraka i banku podataka za gotovo 1000 muškaraca sa bolestima prostate (KP i benigna hiperpla- zija prostate) i preko 350 muškaraca bez znakova bolesti prostate iz populacije Republike Srbije. Naj- veći broj studija bio je dizajniran kao studije asocijacije odabranih genetičkih varijanti sa rizikom za razvoj i progresiju KP. U ovim studijama slučajeva i kontola ispitivane su genetičke varijente kako u ge- nima za proteine i nekodirajuće molekule RNK, tako i u nekodirajućim regionima genoma (tzv. „gen- skim pustinjama“). Pored studija slučajeva i kontrola, sprovođene su i meta-analize kao i analize statističkih epistatičkih interakcija analiziranih genetičkih varijanti. Krajnji cilj ovih studija je kreiranje algoritma za procenu rizika za progresiju bolesti koji bi se koristio u fazi aktivnog praćenja bolesnika sa ranodijagnostikovanim KP. U poslednje vreme, istraživanja su usmerena na egzozome i njihov ma- kromolekulski sadržaj (proteine i nekodirajuće molekule RNK) kao potencijalne biološke markere tečne biopsije KP. Pored toga, biološki makromolekuli na površini egzozoma predstavljaju i ciljane molekule u novim strategijama lečenja KP.

This review-type paper will present the ten-year experience of the PROSTATSERBIA research team, which has the molecular basis of prostate cancer (PCa) as its research topic. The Center for Human Mo- lecular Genetics of the Faculty of Biology, University of Belgrade has a collection of samples and a data bank for almost 1000 men with prostate diseases (PCa and benign prostatic hyperplasia) and for over 350 men without signs of prostate diseases, all from Serbian population. Most of the studies were designed as studies of association of selected genetic variants with the risk for development and progression of PCa. In these case-control studies, genetic variants were examined both in genes for proteins and non-coding RNAs, as well as in non-coding regions of the genome (so-called gene deserts). In addition to case control studies, both meta-analyses and the analysis of statistical epista- tic interactions of the analyzed genetic variants were conducted. The main goal of all these studies was to create an algorithm for risk assessment for disease progression that would be used in the phase of active monitoring of patients with early diagnosed PCa. Recently, we shifted our research focus on exosomes and their macromolecular content (proteins and microRNAs) as potential biological mar- kers of liquid prostate cancer biopsy. In addition, macromolecules at the exosome surface represent target molecules for new PCa treatment strategies.