Izmenjeni nivoi sfingolipidnih metabolita u serumu pacijenata sa lokalno uznapredovalim karcinomom rektuma: pilot studija

Abstract

Background: Altered sphingolipid levels might contribute to rectal cancer development, progression and therapy response by regulating various biological processes, including apoptosis. This study aimed to analyse the serum sphingolipid profile in rectal cancer patients and investigate its association with the apoptotic status of tumour tissue and therapy response. Methods: Ceramide (CER) and sphingomyelin (SM) serum levels were analysed in 22 patients with locally advanced rectal cancer and 24 healthy individuals by ultrafast liquid chromatography coupled with tandem mass spectrometry. The expression of pro-apoptotic BAX (BCL2 associated X, apoptosis regulator) and anti-apoptotic BCL2 (BCL2 apoptosis regulator) was analysed in tumour and corresponding healthy tissue samples of patients by quantitative real-time PCR. Results: Significantly lower serum levels of C18 CER, C22 CER, C24 CER, C18 SM and C24 SM were observed in patients than in controls (P<0.05). For C20 CER, C22 CER and C24 CER, a positive correlation with the pro-apoptotic status of tumour tissue was found (r=0.619, P=0.018; r=0.694, P=0.006 and r=0.601, P=0.023, respectively). No difference in serum sphingolipid levels was found between patients with good, moderate, and poor responses to therapyUvod: Promene u nivou sfingolipida mogu da doprinesu nastanku karcinoma rektuma, progresiji bolesti i odgovoru na terapiju usled njihove regulacije razli~itih biolo{kih pro cesa uklju~uju}i apoptozu. Cilj ove studije je bio da se anali zira profil sfingolipida u serumu kod pacijenata sa karcinomom rektuma i da se ispita njegova povezanost sa apoptotskim statusom tkiva tumora i odgovorom na terapiju. Metode: Nivo ceramida (CER) i sfingomijelina (SM) je ana - liziran u serumu kod 22 pacijenta sa lokalno uznapredova - lim karcinomom rektuma i kod 24 zdrave osobe pomo}u ultrabrze te~ne hromatografije kombinovane sa tandem masenom spektrometrijom. Ekspresija pro-apoptotskog gena BAX (BCL2 asocirjau}i X, regulator apoptoze) i antiapoptotskog gena BCL2 (BCL2 regulator apoptoze) je ana - lizirana pomo}u metode kvantitativni PCR u realnom vremenu u uzorcima tumorskog tkiva i zdrave crevne sluznice kod pacijenata. Rezultati: Nivoi C18 CER, C22 CER, C24 CER, C18 SM i C24 SM su bili zna~ajno ni`i u serumu pacijenata u odnosu na kontrolnu grupu (P<0,05). Za C20 CER, C22 CER i C24 CER je utvr|ena pozitivna korelacija sa pro-apoptotskim statusom tumorskog tkiva (r=0,619, P=0,018; r=0,694, P=0,006 i r=0,601, P=0,023, respektivno). Nije prona|ena razlika u nivoima sfingolipida u serumu izme|u pacijenata sa dobrim, umerenim i lo{im odgovo - rom na terapiju