Otkrivanje prognostičkih čimbenika u bolesnika s karcinomom prostate pomoću proteomske analize tumorskoga tkiva [Discovering prognostic factors in prostate cancer patients using tumor tissue proteomic analysis]

Solak Mekić, Meliha (2019) Otkrivanje prognostičkih čimbenika u bolesnika s karcinomom prostate pomoću proteomske analize tumorskoga tkiva [Discovering prognostic factors in prostate cancer patients using tumor tissue proteomic analysis]. PhD thesis, Sveučilište u Zagrebu.

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Abstract

The biggest obstacle in improving prostatic carcinoma patients' survival rates today is the difficulty of differentiating between indolent and aggressive tumors, caused by the complex and extremely heterogeneous nature of the disease. The objective of this research project was to discover a group of proteins with significantly differing expressions between healthy and tumor tissue, using proteomic analysis, and two-dimensional gel electroforesis (2-DE), together with mass spectrometry. Twelve patients with even samples of healthy and tumor tissue (the Gleason sum: 6(3+3), or 7 (3+4 ili 4+3)) took part. Eighteen differentially exappropriated proteins were singled out as their specific functions made them classifiable either as potential tumor biomarkers, or healthy tissue biomarkers. Proteoms were correlated with relapse frequency and applied oncological treatment. In the participants who were observed to have more aggresive disease, the protein expression was visibly stronger for proteins that were part of the malignant transformation. Additionally, we explored and visually showed the connection between differently produced proteins within each patient's sample pair, using STRING software. Individual carcinoma proteom analysis uncovers a molecular protein-level interaction network. Combined with classic clinical-pathohistological indicators, this offers new insight into every participant's tumor fenotype and stage of advancement.

Abstract in Croatian

Rak prostate složena je i izrazito heterogena bolest što znatno otežava razlikovanje indolentnih od agresivnih tumora te predstavlja najvišu prepreku u poboljšanju preživljenja bolesnika s ovom zloćudnom bolesti. Cilj ovog istraživanja bio je proteomskim analizama, uz pomoć dvodimenzionalne gel elektroforeze (2-DE) u sprezi s spektrometrijom masa, otkriti skupinu proteina čija se ekspresija značajno razlikuje kod karcinoma prostate i zdravog tkiva. Uključeno je dvanaest ispitanika s parnim uzorcima zdravog i tumorskog tkiva Gleasonovog zbroja 6(3+3) ili 7 (3+4 ili 4+3). Od ukupnog broja diferencijalno eksprimiranih proteina izdvojeno je njih 18 zbog njihovih specifičnih funkcija koje ih mogu svrstati u potencijalne tumorske biomarkere ili biomarkere zdravog tkiva. To su: vinkulin, mikrotubul-aktin ukriženo-vežući faktor 1, glioksalaza 1, smotana-uzvojnica domena-sadržavajući protein 168, centromere protein F, tropomiozin alfa-1 lanac, miozin XVIIIB, TPM4-ALK fuzijski onkoprotein tip 2, plazminogen, kiseli leucin-bogati jezgreni fosfoprotein 32A, cink prsten protein 268, centrosomalni protein od 290 KDa, elongacijski faktor Tu, Rho GDP-disocijacijski inhibitor 2, kalumenin, komplement komponenta 1Q subkomponenta-vežući protein, aneksin A1 i transgelin. Nadalje, uspoređeni su proteomi s pojavom recidiva i primijenjenim onkološkim liječenjem. Kod ispitanika s zloćudnijim oblicima bolesti, koji su otkriveni praćenjem, vidljiva je značajnija ekspresija proteina uključenih u malignu transformaciju. Upotrebom STRING programskog alata, dodatno je istražena povezanost razlikovno produciranih proteina unutar parnih uzoraka svakog ispitanika te je napravljen slikovni prikaz pronađenih proteina. Analiza proteoma pojedinačnih karcinoma prostate otkrila je molekularnu mrežu interakcija na razini proteina koja u kombinaciji s klasičnim kliničko-patohistološkim pokazateljima pruža novi uvid u fenotip i agresivnost tumora svakog ispitanika.

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