CAV1 is a potential marker for distinguishing benign prostatic hyperplasia and prostate cancer patients

University of Zagreb School of Medicine

Prostate cancer (PCa) is a highly frequent malignancy in men worldwide. Early detection methods are digital rectal examination and elevated prostate-specific antigen (PSA) levels which are indications for prostate biopsy. PSA is not cancer-specific and the increased level may be caused by other conditions such as benign prostatic hyperplasia (BPH). PSA shows low specificity in screening and diagnostics leading to unnecessary biopsies and health costs. Many asymptomatic PCas with indolent form are detected and treated while clinically significant cases may remain undiagnosed. Therefore, there is a need for a more specific PCa biomarker.

In search of novel non-invasive biomarkers with better performance, researchers from the University of Zagreb School of Medicine, Sestre milosrdnice University Hospital Center and University Hospital Center Zagreb investigated Caveolin-1 (CAV1). CAV1 gene codes protein important for caveolae formation in the plasma membrane and interacts with numerous signaling molecules. Its expression differs between PCa and BPH tissue. DNA methylation is one of the mechanisms for gene expression regulation, thus the researchers focused on CAV1 methylation of cell-free DNA, DNA released from cells, in samples of blood and seminal plasma. The study was performed on 40 patients with a confirmed diagnosis of PCa and 40 patients with a confirmed diagnosis of BPH.

The results revealed that methylation of one CAV1 CpG site in seminal plasma is a potential marker for distinguishing BPH patients and patients with PCa with more indolent tumor course from patients with PCa where more aggressive behavior is expected. However, to enhance diagnostic accuracy, CAV1 methylation should be combined with some other markers in the panel.

Rak prostate (RP) vrlo je čest zloćudni tumor kod muškaraca diljem svijeta. Metode ranog otkrivanja su digitalni rektalni pregled i povišene razine prostata-specifičnog antigena (PSA) što je indikacija za biopsiju prostate. PSA nije specifičan za rak i povećana razina može biti uzrokovana drugim stanjima kao što je benigna hiperplazija prostate (BHP). PSA pokazuje nisku specifičnost u probiru i dijagnostici što dovodi do nepotrebnih biopsija i zdravstvenih troškova. Mnogi asimptomatski slučajevi RP-a s indolentnim oblikom se otkrivaju i liječe dok klinički značajni slučajevi mogu ostati nedijagnosticirani. Stoga postoji potreba za specifičnijim biomarkerom RP-a.

U potrazi za novim neinvazivnim biomarkerima s boljim učinkom, istraživači s Medicinskog fakulteta Sveučilišta u Zagrebu, Kliničkog bolničkog centra Sestre milosrdnice i Kliničkog bolničkog centra Zagreb istraživali su Caveolin-1 (CAV1). Gen CAV1 kodira protein važan za stvaranje kaveola u staničnoj membrani i stupa u interakciju s brojnim signalnim molekulama. Njegova ekspresija se razlikuje između tkiva RP-a i tkiva BHP-a. Metilacija DNA jedan je od mehanizama za regulaciju ekspresije gena, stoga su se istraživači usredotočili na metilaciju gena CAV1 , ali u slobodnoj DNA izvan stanicau uzorcima krvne i sjemene plazme. Istraživanje je provedeno na 40 bolesnika s potvrđenom dijagnozom RP-a i 40 bolesnika s potvrđenom dijagnozom BHP-a.

Rezultati su otkrili da je metilacija jednog CpG mjesta gena CAV1 u sjemenoj plazmi potencijalni marker za razlikovanje bolesnika s BHP-om i pacijenata s RP-om s indolentnijim tijekom tumora od pacijenata s RP-om kod kojih se očekuje agresivnije ponašanje. Međutim, kako bi se povećala dijagnostička točnost, metilaciju gena CAV1 treba kombinirati s nekim drugim markerima u panel.

 

Reference: Škara L, Vodopić T, Pezelj I, Abramovic I, Vrhovec B, Vrtarić A, Sincic N, Tomas D, Bulimbašić S, Kuliš T, Ulamec M. Methylation pattern of Caveolin-1 in prostate cancer as potential cfDNA biomarker. Bosn J of Basic Med Sci [Internet]. 2022Aug.26 [cited 2022Sep.26];. Available from: https://www.bjbms.org/ojs/index.php/bjbms/article/view/7497

Editor: Merima Bukva, MPharm

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