Promjene koncentracija proteina akutne faze i glikozilacije serumskih proteina kod akutne sistematske upale nakon radikalne resekcije kolona

doctoral thesis

• Title (english): Changes in acute phase proteins concentrations and serum proteins glycosylation in acute systematic inflammation after radical colon resection
• Author: Lovorka Đerek
• Mentor: Gordan Lauc (mentor)
• Committee member: Sanja Dabelić (predsjednik povjerenstva)
• Committee member: Dunja Rogić (član povjerenstva)
• Committee member: Neven Ljubičić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of biochemistry and molecular biology); Zagreb
• Defense date and country: 2021, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Medical Biochemistry
• Universal decimal classification (UDC): 615 - Pharmacology. Therapeutics. Toxicology

Abstract

Radikalna resekcija kolona dovodi do procesa akutne upale i sindroma sistemskog upalnog odgovora (engl. systemic inflammatory response syndrome, SIRS). Razina i uzrok SIRS-a nastalog operativnim zahvatima prati se porastom koncentracije proteina akutne faze koji ukazuju na uzrok i tijek upalnog procesa. Sam tijek i individualni odgovor na akutnu upalu nisu u potpunosti razjašnjeni. Upravo zato u u ranoj poslijeoperativnoj fazi sve veću važnost ima i praćenje promjena glikozilacije gdje su utvrđene velike individualne razlike u odgovoru na akutnu sistemsku upalu. Cilj istraživanja je bio ispitati učinak radikalne resekcije kolona na razvoj SIRS-a praćenjem promjena koncentracije sTREM -1, IL-6, prokalcitonina i CRP-a te promjena glikozilacije ukupnih proteina seruma i IgG-a u definiranim točkama mjerenja čime bi se definirala međuovisnost procesa akutne upale i razvoja SIRS-a sa specifičnim promjenama u glikomu i koncentracijama proteina akutne faze.
U istraživanje je uključeno 28 ispitanika (19 muškaraca i 9 žena) medijana dobi 71 godina (44-85) s dijagnozom kolorektalnog karcinoma koji su podvrgnuti radikalnoj resekciji kolona otvorenog tipa. Uzorci krvi uzorkovani su u četiri vremenske točke: 1 dan prije operacije (T0), 24 sata poslije operacije (T1), 48 sati poslije operacije (T2) i 7 dana poslije operacije (T3) kako bi se obuhvatio i akutni odgovor na kirurški stres, ali i popratilo jenjavanje upale ili produljena reakcija na kirurški stres.
Rezultati ovog rada pokazali su statistički značajne promjene sTREM-1, CRP-a, PCT-a i IL-6 kao i N-glikanskih profila ukupnih proteina seruma i N-glikanskih profila IgG-a prije operacije te tijekom 7 dana poslijeoperativnog praćenja ispitanika. Također su utvrđene korelacije IL-6 kao i određenih glikanskih struktura N-glikanskih profila ukupnih proteina seruma i N-glikanskih profila IgG-a s duljinom trajanja operacije. Korelacijskom analizom i linearnom regresijom ispitana je povezanost koncentracija proteina akutne faze s promjenama N-glikanskih profila te su nađene slabe do vrlo dobre korelacije CRP-a, IL-6 i PCT sa specifičnim strukturama od kojih je najjasnija bila korelacija CRP-a s tetragalaktoziliranom i sijaliniziranom strukturom s antenarnom fukozom. sTREM-1 nije pokazao značajnu korelaciju s niti jednim drugim ispitivanim biljegom.
Ovo je istraživanje pokazalo da radikalna resekcija kolona ne dovodi nužno do SIRS-a, a da se tijek i dinamika upale kao odgovora na kirurški stres može pratiti porastom koncentracija proteina akutne faze, pri čemu promjena koncentracija sTREM-1 može ukazati da nije došlo do razvoja SIRS-a. Također se razjasnilo da glikanski profili pokazuju vrlo jasne obrasce promjena koji se mogu povezati s promjenama koncentracija proteina akutne faze te bi se njihovim daljnjim izučavanjem otvorila mogućnost korištenja dobivenih podataka glikanskih profila u svrhu individualnog i sveobuhvatnog praćenja ranog upalnog odgovora.

Abstract (english)

Colorectal cancer surgery, as well as all severe surgical procedures, lead to strong acute phase response and systemic inflammatory response syndrome (SIRS). The extent and the cause of SIRS are monitored with acute phase proteins that point to the cause and course of inflammatory process. The course and the individual response to acute inflammation are not completely understood. In early postoperative phase there is also an increasing importance in monitoring glycosylation changes, where large individual differences have been identified in acute systemic inflammation response. The aim of this study was to test the effect of radical colon resection on SIRS development by monitoring soluble triggering receptor expressed on myeloid cells-1 (sTREM-1), interleukin-6 (IL-6), procalcitonin (PCT) and C-reactive protein (CRP), as well as the changes in N-glycosylation profiles of total serum proteins and immunoglobulin G (IgG) in defined points of measurement that would define interdependence of acute inflammatory process and SIRS development with specific glycome and acute phase proteins changes.
This study included 28 participants (19 men and 9 women) with a median age of 71 years (44-85) and with colorectal cancer diagnosis that underwent radical colon resection. Blood samples were collected in 4 measurement points: 24 hours before the surgery (T0), 24 hours after the surgery (T1), 48 hours after the surgery (T2) and 7 days after the surgery in order to define acute response to surgical stress, as well as to define the decrease of inflammations or notice the extended reaction to surgical stress.
The results showed statistically significant differences of sTREM-1, CRP, IL-6 and PCT, as well as changes in N-glycan profiles of total serum proteins and IgG before the surgery and during 7 days of postoperative recovery. Significant correlations for IL-6, as well as some N-glycan structures of total serum proteins and IgG, were discovered with the duration of the surgery. Correlation and linear regression analysis revealed weak, moderate and very good correlations between CRP, IL-6, PCT and N-glycan profiles of total serum proteins and IgG. The strongest discovered correlation was the very good correlation of CRP with tetragalactosilated and syalinisated structure with antennary fucose. STREM-1 did not reveal any significant correlation with any other tested parameter.
This study showed that radical colorectal cancer surgery does not necessarily lead to SIRS and the course and dynamics of inflammation as the response to surgical stress can be followed by the rise of the acute phase proteins. Changes of sTREM-1 concentrations can indicate that there is no SIRS development. This study also clarified that glycan profiles show very distinct change patterns that can be related to the acute phase proteins concentrations changes. Further research of the glycan profiles could open up the possibility of using the acquired data for individual monitoring of the early inflammatory response.

• Keywords: kolorektalni karcinom; resekcija kolona; odgovor akutne faze; SIRS; glikozilacija
• Keywords (english): colorectal cancer; colon resection; acute phase response; SIRS; glycosylation
• Language: croatian
• URN:NBN: urn:nbn:hr:163:759919
• Promotion: 2021
• Study programme: Title: Pharmacy and biochemistry; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor znanosti (doktor znanosti)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2021-05-19 12:08:47