Izraženost i klinički značaj galektina-3, VEGF-a i NF-κB u difuznom B-velikostaničnom limfomu

doctoral thesis

• Title (english): Expresion and clinical importance of galektin-3, VEGF and NF-κB in diffuse large B-cell lymphoma
• Author: Sandra Bašić-Kinda
• Mentor: Igor Aurer (mentor)
• Committee member: Vlatko Pejša (predsjednik povjerenstva)
• Committee member: Slavko Gašparov (član povjerenstva)
• Committee member: Slobodanka Ostojić Kolonić (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; Zagreb
• Defense date and country: 2023-06-12, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Pathology
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Internal Medicine
• Universal decimal classification (UDC): 616 - Pathology. Clinical medicine

Abstract

Uvod i svrha rada: Galektin-3 je jedini galektin kimerične strukture. Uključen je u važne stanične procese: regulaciju proliferacije stanica, apoptozu i angiogenezu.Više od 50% DLBCL-a izražava galektin-3. Preliminarni rezultati pokazuju da galektin-3 + DLBCL ima lošiju prognozu. Svrha je ovog rada usporediti biološke i kliničke karakteristike galektin3+ i galektin-3- DLBCL-a i ishode liječenja.
Materijali i metode: U novodijagnosticiranih bolesnika s DLBCL-om, liječenih R-CHOP-om ili sličnim protokolom analizirali smo kliničke karakteristike (dob, spol, IPI, odgovor na liječenje, EFS i OS). Imunohistokemijski smo odredili izražaj galektina-3, BCL2, VEGF i NF-κB i stanično podrijetlo tumora. Rezultati: Uključeno je ukupno123 bolesnika uz medijan praćenja 68 mjeseci. Galektin-3 bio je pozitivan kod 69 (56,1%). Bolesnici koji su imali viši IPI (p=0,002), ABC fenotip (p=0,029) i pojačani izražaj NF-κB (p=0,016) češće su izražavali galektin-3. Izražaj galektina 3 nije značajno utjecao na OS i EFS. BCL2 + bolesnici imali su značajno lošiji ishod ukoliko su istovremeno bili galektin3+ (dvogodišnji EFS 44% vs 73% (p=0,002) i OS 50% vs 74% (p=0,006). Značajno više VEGF + tumora imalo je ABC fenotip. Značajno lošiji ishod imali su VEGF+ DLBCL GCB ali ne i ABC imunofenotipa (p=0,001).U multivarijatnoj analizi BCL2 je bio jedini značajni faktor za EFS i OS, dok izražaj galektina-3 pokazuje trend za lošiji ishod (p=0,068 za EFS i p=0,093 za OS).
Zaključak: Naši rezultati u skladu su s eksperimentalnim podacima koji pokazuju da NF-κB stimulira izražaj galektina-3 i da galektin-3 dodatno potencira antiapoptotički učinak BCL2. Galektin-3 je češće izražen kod uznapredovalog stadija DLBCL-a i kod ABC fenotipa, što je u skladu s njegovim potencijalnim proliferativnim i antiapoptotičkim učinkom i njegovim izražajem na memorijskim stanicama.

Abstract (english)

Introduction and aim: Galektin-3 is the only chimeric galectins. It is involved in crucial cellular processes including cell proliferation, apoptosis and angiogenesis. More than 50% of DLBCL express galectin-3. Preliminary results showed that galectin 3+ DLBCL have inferior prognosis. The purpose of this study is to compare biological and clinical characteristics of galectin-3+ and galectin-3- DLBCL and outcomes of treatment.
Material and methods: In newly diagnosed DLBCL patients treated with R-CHOP like regimens we analyzed clinical characteristics (age, sex, IPI, response to treatment, EFS and OS). Expression of gal-3, BCL2, VEGF and NF-κB and cell of origin were determined by immunochemistry.
Results: 123 patients were included with a median follow up 68 months. Galectin-3 was positive in 69 (56,1%). Patient with high IPI (p=0,002), ABC phenotype (p=0,029) and NF-κB + (p=0,016) expressed galektin-3 more frequently. Expression of galektin-3 did not affect OS and EFS. BCL2 + patients fared significantly worse if they coexpressed galektin-3 (2-y EFS 44% vs 73% (p=0,002) and OS 50% vs 74% (p=0,006)). Significantly higher number of VEGF + tumors were of ABC origin. Outcomes of VEGF + GCB, but not ABC DLBCLs were significantly inferior (p=0,001). In multivariant analysis BCL2 was only significant factor for EFS and OS, while galectin-3 showed trend for worse outcomes (p=0,068 for EFS and p=0,093 for OS).
Conclusion: Our results are consistent with experimental data showing that NF-KB stimulates galectin-3 expression and that galectin-3 potentiates antiapoptotic effect of BCL2. Galectin-3 is more commonly expressed in advanced stage DBCL and also in ABC phenotype, which is in accordance with his potential proliferative and antiapoptotic effect and its expression on memory cells.

• Keywords: Galektin-3; Galektin-3; NF-κB; Imunokemija; Vinkristin; Rituksimab; Ciklofosfamid; Proliferacija stanica
• Keywords (english): Galectin-3; NF-κB; Immunochemistry; Vincristine; Rituximab; Cyclophosphamide; Cell Proliferation
• Language: croatian
• URN:NBN: urn:nbn:hr:105:092923
• Study programme: Title: Biomedicine and Health Sciences; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor/doktorica znanosti, područje biomedicine i zdravstvo (doktor/doktorica znanosti, područje biomedicine i zdravstvo)
• Type of resource: Text
• Extent: 81 str.
• File origin: Born digital
• Access conditions: Open access
• Created on: 2023-07-07 09:43:09