Abstract | Sfingolipidi predstavljaju važne komponente membrana eukariotskih stanica, stoga imaju ulogu u regulaciji brojnih staničnih signalnih puteva. U ovom završnom radu cilj je utvrditi koji bioaktivni sfingolipidi i njihovi metabolički enzimi mogu služiti kao potencijalni dijagnostički, prognostički i prediktivni biomarkeri u nekoliko tipova raka, uključujući rak jetre, debelog crijeva i dojke. Biomarkeri su po definiciji objektivne, kvantificirajuće karakteristike bioloških procesa stoga su važni za pravovremeno otkrivanje, dijagnozu, prevenciju te uspješno liječenje bolesti. Brojne su studije pokazale značajnu povezanost između metabolizma sfingolipida i kliničkog ishoda bolesti. Takvi rezultati daju veliku važnost sfingolipidima kao biomarkera u dijagnozi i prognozi raka. Kako bi se uspješno otkrila složena patofiziologija uključena u rak te put genetskih promjena stanica raka, potreban je širok raspon različitih sfingolipidnih biomarkera za poboljšanje osjetljivosti i specifičnosti biomarkera potrebne za istraživanje. Pri tome se naglasak stavlja na pro-apoptotički ceramid, pro-proliferitativni sfingozin, ceramid-1-fosfat (C1P), sfingozin-1-fosfat (S1P) te na brojne enzime koji sudjeluju u metabolizmu sfingolipida. Stoga će poremećaj metabolizma i sfingolipidnog reostata u organizmu dovesti do gubitka optimalne razine sfingolipida što upućuje na razvoj kancerogenog stanja. |
Abstract (english) | Sphingolipids are important components of eukaryotic cell membranes that have a role in regulating numerous cellular signals. In this final assignment, the aim is to determine which bioactive sphingolipids and their metabolic enzymes can be potential diagnostic, prognostic, and predictive biomarkers in several types of cancer, including liver, colon, and breast cancer. Biomarkers are by definition objective, quantifiable characteristics of biological processes and therefore important for early detection, diagnosis, prevention, and successful treatment of the disease. Numerous studies show a significant association between sphingolipid metabolism and clinical disease outcomes. Such results give big importance to sphingolipids as biomarkers in the diagnosis and prognosis of cancer. Successful determination of complex pathophysiology involved in cancer and genetic change in cancer cells, demands the use of panel of different sphingolipid biomarkers to improve sensitivity and specificity of biomarkers needed for research. Emphasis is on the use of pro-apoptotic ceramide, pro-proliferative sphingosine, ceramide-1-phosphate (C1P), sphingosine-1-phosphate (S1P), and numerous enzymes involved in the metabolism of sphingolipids. Therefore, disruption of metabolism and sphingolipid rheostat in the organism will lead to loss of optimal sphingolipid levels leading to the development of a cancerous condition. |