20.500.12556/DKUM-19331 ANALIZA EKSPRESIJE IZBRANIH KANDIDATNIH GENOV POVEZANIH Z RAKOM ŠIROKEGA ČREVESA IN DANKE PRI BOLNIKIH S KRONIČNO VNETNO ČREVESNO BOLEZNIJO IN PRI BOLNIKIH S ČREVESNIMI POLIPI GENE EXPRESSION ANALYSIS OF SELECTED COLORECTAL CANCER CANDIDATE GENES IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE AND IN PATIENTS WITH COLORECTAL POLYPS Izsledki raziskav zadnjih let nakazujejo na povečano tveganje nastanka raka širokega črevesa in danke (RŠČD) pri bolnikih s kronično vnetno črevesno boleznijo (KVČB). Naša temeljna predpostavka je bila, da so geni, vpleteni v zgodnjo fazo razvoja RŠČD pri bolnikih s KVČB, izraženi na podoben način v tkivnih vzorcih polipov ŠČD in vneti sluznici bolnikov s KVČB. Z bioinformatskimi orodji smo identificirali 5 kandidatnih genov (BAX, IFITM3, COX-2, TLR4 in LRP6) in analizirali njihovo ekspresijo pri bolnikih s KVČB in bolnikih s črevesnimi polipi. Za vsakega bolnika smo analizirali ekspresijo izbranih genov v prizadetem tkivu v primerjavi z normalnim tkivom pri istem bolniku. Za štiri od petih kandidatnih genov (IFITM3, COX-2, TLR4 in LRP6) smo dokazali statistično značilno spremenjeno ekspresijo pri bolnikih s polipi ŠČD in pri bolnikih s Crohnovo boleznijo (CB). V tem smislu smo potrdili hipotezo, da imajo geni, vpleteni v zgodnjo fazo karcinogeneze kronično vnetega črevesnega tkiva, signifikantno spremenjeno ekspresijo v nevnetem polipoznem črevesnem tkivu pri bolnikih s polipi ŠČD, kakor tudi v vnetem črevesnem tkivu pri bolnikih s KVČB. Nadalje smo določili skupino bolnikov s CB, ki imajo podoben vzorec izražanja izbranih genov kot bolniki s črevesnimi polipi, na podlagi ujemanj v ekspresiji smo ustvarili podskupino bolnikov s CB, ki ima potencialno večje tveganja za razvoj raka ŠČD. 60% CB bolnikov ima signifikantno spremenjeno ekspresijo dveh kandidatnih genov, 20% bolnikov s CB ima signifikantno spremenjeno ekspresijo treh kandidatnih genov in pri 5% bolnikov s CB je ekspresija signifikantno spremenjena pri vseh štirih kandidatnih genov. Skupina bolnikov, ki imajo podoben vzorec izražanja izbranih genov imajo verjetno povečano tveganje za začetek procesov nastanka novotvorb. Recent studies have indicated a clear link between chronic inflammation and somatic mutations and consequently, increased risk of cancer. Our hypothesis was that genes which are found to be involved in an early stage of IBD-associated cancer development are expressed in a similar manner in the polypoid tissue samples of patients with colorectal polyps and in the inflamed tissue of IBD patients. We studied the gene expression in the affected tissue compared with the normal tissue in the same patient. With bioinformatic tools, we identified five candidate genes. 4 out of 5 candidate genes showed significantly altered expression in polypoid tissue from patients with colorectal polyps and in inflamed tissue from patients with Crohn disease (CD) (IFITM3, COX-2, TLR4 and LRP6). In this context, we have confirmed that genes which are involved at an early stage of IBD-associated carcinogenesis, have significantly altered expression in polypoid intestinal tissue from patients with colorectal polyps as well as in inflamed intestinal tissue from patients with IBD. Furthermore, we defined a subgroup of CD patients with similar patern of expression of the candidate genes as the group of patients with colorectal polyps. Two candidate genes had significantly altered expression in 60% of CD patients, 20% of CD patients had significantly altered expression in 3 of the candidate genes, and in 5% of CD patients we have found all 4 of the candidate genes to be significantly expressed. CD patients show similar patern of expression of the candidate genes and have potentially increased risk of developing neoplastic transformation. Kronična vnetna črevesna bolezen polipi kolorektuma genska ekspresija PCR v realnem času Inflammatory bowel disease colorectal polyps gene expression real time PCR true true false [E. Gjorgievska] Slovenski jezik Angleški jezik Diplomsko delo 2011-07-05 14:40:52 2011-07-18 09:53:28 2022-04-13 15:17:21 2023-12-25 03:16:00 2011 0 Maribor 0 0000-00-00 NiDoloceno NiDoloceno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 616.34-006 4004159 URN:SI:UM:DK:MHHXWYSS UNI_Gjorgievska_Elena_2011.pdf UNI_Gjorgievska_Elena_2011.pdf 1 D6B8CA017C91F3E16FA1C8D7063005C9 a02a43f2e2bb6f21f58c222c9da3f2eb3f32a471f6309398eaf9ad9f2ffce564 62a17a50-7c05-11eb-bb7a-00155d0001ca 20.500.12556/dkum/03490f04-8755-49cf-9ffe-a54f3e6bbac3 https://dk.um.si/Dokument.php?lang=slv&id=23557 Fakulteta za kemijo in kemijsko tehnologijo 0 0 0