Dijagnostički značaj proteina oštećenja bubrega-1 (KIM-1) i akvaporina 1 (AQP-1) kod bolesnika koji boluju od karcinoma svetlih ćelija bubrega

Abstract

Karcinom bubrega (KB) čini približno 3,8% od ukupnog broja maligniteta kod odraslih, pokazujući konstantan porast poslednjih 30 godina. Najčešći i najagresivniji podtip KB je svetloćelijski karcinom bubrega (sKB), koji se često karakteriše odsustvom ranih simptoma i znakova bolesti, kao i laboratorijskih abnormalnosti. Pouzdan urinarni test za sKB mogao bi da ima značaj u preoperativnoj dijagnozi ovog tumora i kao dodatni marker za odgovor na terapiju i post-terapijsko praćenje. Sprovedena ispitivanja su ukazala na povećanu ekspresiju određenih proteina u tumorskom tkivu sKB. Na osnovu potencijala za urinarnu ekskreciju ovih ushodno regulisanih proteina, kao i senzitivnosti i specifičnosti za dijagnozu sKB, izdvojili su se protein 1 oštećenja bubrega (KIM-1) i akvaporin 1 (AQP-1). Cilj studije je bio da se ispita potencijal KIM-1 i AQP-1 za dijagnozu sKB, posebno tumorskih promena promera do 4 cm, kao i povezanost njihove koncentracije u urinu sa histološkim karakteristikama tumora. U studiju je bio uključen 41 pacijent (26 muškaraca, 15 žena), kod kojih je nakon parcijalne ili radikalne nefrektomije postavljena dijagnoza sKB. Kontrolnu grupu činilo je 40 zdravih ispitanika. Koncentracija oba biomarkera u urinu određena je primenom komercijalnog ELISA testa. Ekspresija KIM-1 u tumorskom tkivu određena je primenom TIM-1/KIM-1/HAVCR antitela. Rezultati ove studije su pokazali da određivanje koncentracije KIM-1 u urinu kod pacijenata sa sumnjom na postojanje sKB, predstavlja senzitivan i specifičan test za preoperativnu dijagnozu bolesti i da značajno korelira sa stadijumom i gradusom tumora. Određivanje koncentracije KIM-1 u urinu predstalja dodatni dijagnostički test za utvrđivanje prirode malih tumorskih promena promera do 4 cm. Poređenjem koncentracija KIM-1 u urinu izraženim u apsolutnim i korigovanim vrednostima, nije pokazana statistički značajna razlika u dijagnostičkom potencijalu. Tkivna ekspresija KIM-1 statistički značajno korelira sa stadijumom tumora i visoko korelira sa gradusom tumora ali bez statističke značajnosti. Koncentracija AQP-1 u urinu je nedovoljno senzitivan i specifičan test za dijagnozu karcinoma svetlih ćelija bubrega.

Renal cell carcinoma (RCC) represents approximately 3.8% of all malignancies in adults, increasing permanently over the past 30 years. The most common and also the most aggressive subtype of RCC is clear renal cell carcinoma (cRCC), often characterized by lack of early symptoms, signs and laboratory abnormalities. A reliable urine test for cRCC could have importance in the preoperative diagnosis of this tumor as an additional marker for the monitoring of response to therapy and for the post-treatment surveillance, as well. Recent studies have shown the increased expression of certain proteins in tumor tissue of cRCC. Based on the potential for urinary excretion of these up-regulated proteins, as well as the sensitivity and specificity for the diagnosis of cRCC, the kidney injury molecul 1 (KIM-1) and aquaporin 1 (AQP-1) have a special significance. The aim of this study was to investigate the potential of KIM-1 and AQP-1 for the diagnosis of cRCC, especially lesion diameter up to 4 cm, and the linkage of their concentration in urine and histological characteristics of the tumor. The study involved 41 patients (26 men, 15 women), who underwent the partial or radical nephrectomy and diagnosed cRCC. The control group consisted of 40 healthy subjects. The concentration of both biomarkers in the urine was determined by commercially available ELISA kits. Expression of KIM-1 in the tumor tissue is determined by applying the TIM-1/KIM-1/HAVCR antibody. Results of this study showed that the determination of the concentration of KIM-1 in the urine of patients with suspected cRCC is sensitive and specific test for the preoperative diagnosis of the disease and significantly correlated with tumor stage and grade. Determination of KIM-1 in urine represented a further diagnostic test to determine the nature of small lesion sizes up to 4 cm. By comparing the concentration of KIM-1 in urine expressed in absolute and corrected values, we did not show statistically significant difference in the diagnostic potential. Tissue expression of KIM-1 is significantly correlated with tumor stage and highly correlated with tumor grade but without statistical significance. The concentration of AQP-1 in urine was insufficiently sensitive and specific test for diagnosis of cRCC.