Pseudokolinesteraza i pokazatelji oksidacijskoga stresa u djece s tumorskom bolešću u središnjem živčanom sustavu

Mikecin, Lili (2017) Pseudokolinesteraza i pokazatelji oksidacijskoga stresa u djece s tumorskom bolešću u središnjem živčanom sustavu. PhD thesis, Sveučilište u Zagrebu.

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Abstract

The aim of the study is to determine the activity of pseudocholinesterase (PChE) in serum and cerebrospinal fluid (CSF) and oxydative stress enzymes superoxide dismutase (SOD), catalase (CAT) and glutation peroxidase (GPx) in CSF and blood in children with solid central nervous system (CNS) tumor and to assess whether PChE activity and SOD, CAT and GPx could be a valid biomarker for solid CNS tumors in children. One of the final products of lipid peroxidation is malodialdehide (MDA) was determined too. Methods: The study and control group included 30 children each. Children in the study group had a solid CNS tumor, while those from the control group had never suffered from any tumor diseases. CSF and blood samples were collected from all participants. PChE activity was determined using the Ellman’s spectrophotometric method. GPx, SOD and CAT activity were measured spectrophotometrically; MDA with HPLC method. PChE activity in CSF was shown as a cerebrospinal fluid/serum ratio expressed in percentage, ie, PChE CSF/serum ratio. Receiver operating characteristic (ROC) curve was used to assess whether PChE activity, SOD, CAT and GPx can be used as a biomarker for identifying children with solid CNS tumors. Results: Children with solid CNS tumor had significantly higher PChE activity in CSF and serum, as well as PChE CSF/serum ratio (P= 0.001). PChE CSF/serum ratio in the study group was 2.38% (interquartile range [IQR] 1.14-3.97) and 1.09% (IQR 0.95-1.45) in the control group. ROC curve. analysis of PChE CSF/serum ratio resulted in an area under the curve (AUC) value of 0.76 (95% confidence interval [CI] 0.63-0.88) and a cut-off of 1.09. Twenty five of 29 patients with elevated PChE CSF/serum ratio had a tumor, corresponding to a sensitivity of 83% and a specificity of 53%. SOD, CAT, GPx and MDA in CSF have high specifity and sensitivity for the solid brain tumors in children and this study provide a cutt of values for the each of them. Between antioxidants highest sensitivity in plasma has SOD 84.62%; highest specifity has GPx 75%. In CSF highest sensitivity showed GPx 89.29%, highest specifity has SOD 100%. MDA sensitivity in brain tumor children in plasma is 80% and in CSF 70%. It’s specificity for plasma is 85.19% and in CSF 78.57%. SOD in plasma resulted in AUC 0,51 and in CSF 0,91; GPx in plasma 0,85 in CSF 0,93; CAT in plasma 0,69 and in CSF 0,90; MDA in plasma 0,89 in CSF 0,78. Conclusion: PChE CSF/serum ratio and SOD, CAT and GPx in CSF resulted in AUC from 0,80 to 0,93 and may be used as a biomarkers with good sensitivity and good or excellent tests for solid CNS tumors in children.

Abstract in Croatian

Cilj studije je odrediti aktivnost pseudokolinesteraze (PChE) i enzima oksidacijskog stresa superoksid dizmutaze (SOD), katalaze (CAT) i glutation peroksidaze (GPx) u likvoru i krvi djece sa solidnim tumorom središnjeg živčanog sustava (SŽS) kako bi se ustanovilo jesu li aktivnosti PChE, SOD, CAT i GPx valjani biomarkeri za solidne tumore SŽS u djece. Određen je i malondialdehid (MDA) kao jedan od krajnjih produkata lipidne peroksidacije. Metode: Glavna i kontrolna skupina ispitanika imale su svaka po 30 ispitanika. Djeca glavne skupine imala su solidni tumor SŽS, dok ona iz kontrolne skupine nisu nikada bolovala od tumorske bolesti. Svim ispitanicima uzeti su uzorci krvi i likvora. SOD, GPx i CAT su određeni spektrofotometrijski; MDA aktivnost HPLC metodom, PChE metodom po Ellmanu. PChE aktivnost u likvoru je prikazana kao PChE likvor/serum omjer izražen u postocima. Receiver operating characteristic (ROC) krivulje su korištene kako bi se utvrdilo jesu li PChE, SOD, CAT, GPx aktivnosti valjani biomarkeri za identifikaciju djece sa solidnim tumorom SŽS. Rezultati: Djeca sa solidnim tumorom središnjeg živčanog sustava imaju sigifikantno višu aktivnost PChE u likvoru i serumu, kao i PChE likvor/serum omjer (P=0.001). PChE likvor/serum omjer u glavnoj skupini je 2.38% (interkvartilni opseg [IQR] 1,14-3,97) i 1,09% (IQR 0,95-1,45) u kontrolnoj skupini. Analiza ROC krivulje PChE likvor/serum omjera pokazala je vrijednost prostora ispod krivulje (AUC) od 0,76 (95% interval pouzdanosti (eng. confidence interval) [CI] 0,63-0,88) i granična vrijednost (eng. cut-off) od 1,09. Dvadeset pet od 29 bolesnika s visokim omjerom PChE likvor/serum je imalo tumor SŽS i pokazuje senzitivnost od 83% i specifičnost 53%. SOD, CAT, GPx i MDA u likvoru pokazuju visoku specifičnost i senzitivnost za solidne tumore središnjeg živčanog sustava u djece. Studija pruža granične vrijednosti za svaku od njih. Između antioksidansa, najveću senzitivnost u plazmi pokazuje SOD od 84,62%; najvišu specifičnost GPx od 75%. U likvoru najvišu senzitivnost pokazuje GPx od 89,29%, najvišu specifičnost SOD od 100%. MDA ima senzitivnost od 80,0% u plazmi te 70,0% u likvoru. Njegova specifičnost kao biomarkera iz plazme je 85,19% a za likvor 78,57%. Prostor ispod krivulje (AUC) za SOD u plazmi je 0,51; u likvoru 0.91. Za GPx u plazmi 0,85, u likvoru 0,93; za CAT u plazmi 0,69, u likvoru 0,90; MDA u plazmi 0,89 i likvoru 0,78. Zaključak: Omjer PChE likvor/serum i SOD, CAT i GPx likvoru pokazuju opseg AUC od 0,80 do 0,93 što mjeri točnost testa i stavlja ga statistički u skupinu dobrog ili i izvrsnog tako da se mogu upotrijebiti kao biomarkeri sa dobrom senzitivnošću za solidne tumore središnjeg živčanog sustava u djece.

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