Prognostičko značenje izražaja gena za citokeratin-20 u stanicama periferne krvi bolesnika s rakom debeloga crijeva

doctoral thesis

• Title (english): Cytokeratin-20 positive cells in blood of colorectal cancer patients as a prognostic marker
• Author: Davor Kust
• Mentor: Ivan Šamija (mentor)
• Committee member: nije dostupno (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; Zagreb
• Defense date and country: 2016-07-05, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences
• Universal decimal classification (UDC): 61 - Medical sciences

Abstract

Citokeratin 20 (CK20) jedan je od najistraživanijih biljega za detekciju
cirkulirajućih tumorskih stanica. Detekcija cirkulirajućih tumorskih stanica pomoću
lančane reakcije polimerazom nakon reverzne transkripcije (RT-PCR) istraživana je kao
prognostički biljeg u bolesnika oboljelih od raka debelog crijeva u nekoliko studija, ali
za sada s oprečnim rezultatima u pogledu prognostičke vrijednosti. Osnovni cilj ovog
istraživanja bio je odrediti prognostičku vrijednost detekcije cirkulirajućih stanica
metodom RT-PCR za biljeg CK20.
Ribonukleinska kiselina (RNA) je izolirana iz mononuklearne frakcije uzoraka
krvi dobivenih od 95 bolesnika s rakom deblog crijeva prije i nakon operativnog
zahvata te od 23 zdrava dobrovoljca. Izražaj CK20 određen je metodom RT-PCR u
stvarnom vremenu.
Među 23 zdrava dobrovoljca, sedam ih je bilo pozitivno na CK20. Među 95
bolesnika oboljelih od kolorektalnog karcinoma, 69 ih je bilo pozitivno na CK20 prije, a
74 nakon operacije. Petnaest bolesnika pozitivnih prije operacije postalo je negativno
nakon zahvata, dok je 20 bolesnika koji su preoperativno bili CK20 negativni postalo
pozitivno postoperativno. Povećan udio CK20 pozitivnih uzoraka u višim stadijima
bolesti uočen je kod postoperativnih, ali ne i preoperativnih uzoraka krvi. Bolesnici koji
su postoperativno bili CK20 pozitivni imali su statistički značajano kraće vrijeme do
progresije bolesti (PFS) i ukupno preživljenje (OS) u usporedbi s bolesnicima
negativnima na CK20 postoperativno, dok razlika između CK20 pozitivnih i negativnih
bolesnika preoperativno nije bila statistički značajna u pogledu PFS-a i OS-a.
Navedeni rezultati pokazuju da CK20 kao biljeg cirkulirajućih stanica raka ima
prognostičku vrijednost u bolesnika oboljelih od kolorektalnog karcinoma. U
slučajevima kada je prisutno više mogućih terapijskih opcija, bolesnici s pozitivnim
postoperativnim izražajem CK20 bi mogli biti kandidati za agresivnije liječenje.

Abstract (english)

Cytokeratin 20 (CK20) is one of the most investigated markers for the detection
of circulating cancer cells. Detection of circulating cancer cells by reverse transcription
polymerase chain reaction (RT-PCR) was studied as prognostic marker in colorectal
cancer patients in several studies, but so far with conflicting results regarding its
prognostic value. Primary aim of this study was to evaluate prognostic value of RTPCR
detection of circulating colorectal cancer cells using CK20 as a marker.
Ribonucleic acid (RNA) was isolated from mononuclear cell fraction of blood
samples taken from 95 colorectal cancer patients before and after tumor resection, and
from 23 healthy volunteers, and assayed by real-time RT-PCR for CK20 expression.
Among 23 healthy volunteers, seven were positive for CK20. Among 95
colorectal cancer patients, 69 were positive for CK20 before, and 74 after surgery.
Fifteen patients positive before surgery became negative after surgery, while 20 patients
negative before surgery became positive after surgery. Increase in the proportion of
CK20 positive samples with increasing stage of disease was observed for postoperative,
but not for preoperative blood samples. In patients positive for CK20 postoperatively,
both progression-free survival (PFS) and overall survival (OS) were statistically
significantly shorter in comparison to patients negative for CK20 postoperatively and
difference between patients CK20 positive and negative preoperatively was not
statistically significant in terms neither PFS nor OS.
Our results have shown that CK20 as marker for detection of circulating cancer
cells has a prognostic value in colorectal cancer patients. In cases where multiple
treatment options are possible, patients with positive postoperative CK20 expression
could be candidates for more aggressive treatment.

• Keywords: medicina
• Keywords (english): medicine
• Language: croatian
• URN:NBN: urn:nbn:hr:105:436692
• Study programme: Title: Biomedicine and Health Sciences; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor/doktorica znanosti, područje biomedicine i zdravstva (doktor/doktorica znanosti, područje biomedicine i zdravstva)
• Type of resource: Text
• Extent: 102 str.
• File origin: Born digital
• Access conditions: Open access
• Created on: 2023-05-05 08:07:20