Izraženost DVL2 i DVL3 proteina u difuznim karcinomima želuca

master's thesis

• Title (english): DVL2 and DVL3 protein expression in diffuse gastric carcinomas
• Author: Marija Perković
• Mentor: Tamara Nikuševa Martić (mentor)
• Committee member: Frane Paić (predsjednik povjerenstva)
• Committee member: Ljiljana Šerman (član povjerenstva)
• Committee member: Tamara Nikuševa Martić (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; (Department of Medical Biology); Zagreb
• Defense date and country: 2018-07-13, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Basic Medical Sciences; Immunology

Abstract

Karcinom želuca jedan je od najčešćih tumora na svjetskoj razini, a praćen je visokom razinom smrtnosti. Prema Laurenovoj klasifikaciji iz 1965. godine postoje dva glavna histološka tipa adenokarcinoma želuca, intestinalni i difuzni tip. Genetska podloga ovih karcinoma još uvijek je nedovoljno istražena, a posebno mutacije koje dovode do nastanka difuznog tipa karcinoma želuca. Wnt signalni put uključen je u razvoj različitih vrsta tumora, kao i proteini obitelji Dishevelled koji su njegovi nizvodno smješteni medijatori. Cilj ovog rada bio je analizirati izraženost DVL2 i DVL3 proteina u difuznim karcinomima želuca, s pretpostavkom kako bi oni mogli imati važnu ulogu u razvoju te vrste karcinoma. Ekspresija DVL2 proteina analizirana je u 41 kontrolnom uzorku zdravog tkiva želuca te u 49 uzoraka difuznih karcinoma želuca. Ekspresija DVL3 proteina analizirana je u 49 kontrolnih uzoraka zdravog tkiva želuca te u 50 uzoraka difuznih karcinoma želuca. Uzorci su prikupljeni iz arhive Kliničkog zavoda za patologiju i citologiju KBC-a Zagreb. Nakon imunohistokemijskog bojenja, u kojem su korištena primarna poliklonska protutijela DVL2 i DVL3, rezultati su analizirani semikvantitativnom metodom uz bodovanje postotka pozitivnih tumorskih stanica i intenziteta bojenja. Ekspresija DVL2 proteina u tumorskom tkivu bila je statistički značajno jača u odnosu na zdravo tkivo želuca (p=0.0066). Nasuprot tomu, ekspresija DVL3 proteina nije pokazala statistički značajno jaču ekspresiju u tumorskom tkivu u usporedbi sa zdravim tkivom želuca (p=0.1308). Ekspresija DVL3 proteina statistički je značajno veća u odnosu na DVL2 protein u tumorskom tkivu (p=0.0022), kao i u zdravom tkivu želuca (p<0.0001). Dobiveni rezultati ukazuju da bi DVL2 mogao imati važnu ulogu u razvoju ove vrste karcinoma. Potrebne su daljnje studije koje bi tu ulogu razjasnile i proučile mogućnost korištenja DVL2 proteina kao tumorskog markera u dijagnostici ili kao ciljne molekule za djelovanje terapije u difuznim karcinomima želuca.

Abstract (english)

Gastric cancer is one of the most common cancers worldwide, accompanied with high death rate. According to Lauren classification, introduced in 1965, the gastric cancer is classified into two major histological subtypes, intestinal and diffuse type. There is insufficient information concerning genetic abnormalities involved in the pathogenesis of these carcinomas, in particular diffuse type adenocarcinoma. The Wnt signaling pathway and its central mediators, called Dishevelled proteins, play an important role in the development of numerous tumor types. The aim of this study was to analyze DVL2 and DVL3 protein expression in diffuse gastric carcinomas, that we assumed could have potential role in their development. DVL2 expression was analyzed in 41 sample of healthy stomach tissue, as well as in 49 samples of diffuse gastric carcinomas. DVL3 expression was analyzed in 49 samples of healthy stomach tissue, as well as in 50 samples of diffuse gastric carcinomas. The samples were collected from the archives of the Department of Pathology and Cytology of the Zagreb University Hospital Center. After immunohistochemical staining with primary polyclonal antibodies DVL2 and DVL3, the results were analyzed with semiquantitative method which combined the percentage of positive cells and staining intensity. DVL2 protein expression was higher in tumor tissue compared to healthy stomach tissue (p=0.0066). However, DVL3 protein expression was not statistically significantly higher in tumor tissue compared to healthy stomach tissue (p=0.1308). DVL3 expression compared to DVL2 expression was statistically significantly higher in tumor tissue (p=0.0022), as well as in healthy stomach tissue (p<0.0001). The results indicate that DVL2 might have an important role in development of these type of carcinomas. The further studies are required to clarify this role and to define the possibility of using DVL2 as tumor marker or as target molecule for diffuse gastric carcinoma therapy.

• Keywords: difuzni karcinom želuca; Wnt signalni put; Dishevelled proteini; DVL2; DVL3; genske promjene
• Keywords (english): diffuse gastric carcinoma; Wnt signaling pathway; Dishevelled proteins; DVL2; DVL3; genetic abnormalities
• Language: croatian
• URN:NBN: urn:nbn:hr:105:598969
• Study programme: Title: Medicine; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: doktor/doktorica medicine (doktor/doktorica medicine)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2019-01-10 12:26:08