Title IZRAŽAJ RIBONUKLEARNOG PROTEINA IMP3 U KANCEROGENEZI SKVAMOZNOG EPITELA GRKLJANA
Title (english) THE EXPRESSION OF RIBONUCLEAR PROTEIN IMP3 IN CANCEROGENESIS OF SQUAMOUS EPITHELIUM IN LARYNX
Author Diana Maržić
Mentor Tamara Braut (mentor)
Mentor Manuela Avirović (komentor)
Committee member Dražen Kovač (predsjednik povjerenstva) MBZ: 161914
Committee member Drago Prgomet (član povjerenstva)
Committee member Ester Pernjak-Pugel (član povjerenstva)
Committee member Tamara Braut (član povjerenstva)
Committee member Manuela Avirović (član povjerenstva)
Granter University of Rijeka Faculty of Medicine (Department of Otorhinolaryngology) Rijeka
Defense date and country 2020, Croatia
Scientific / art field, discipline and subdiscipline BIOMEDICINE AND HEALTHCARE Clinical Medical Sciences
Universal decimal classification (UDC ) 616 - Pathology. Clinical medicine
Thesaurus (MESH - Medical Subject Headings )
Laryngeal Neoplasms
Carcinoma, Squamous Cell
Insulin-Like Growth Factor Binding Protein 3
Tumor Suppressor Protein p53
Prognosis
Abstract Uvod: Skvamozni karcinom (SCC) grkljana predstavlja više od 95% malignih tumora grkljana. IMP3 je onkofetalni RNK vežući protein koji je kao biobiljeg povezan s uznapredovalošću niza malignih tumora i koristan za stupnjevanje displastičnih lezija. Pregledom dostupne znanstvene literature, utvrdili smo da postoji svega jedan znanstveni rad koji se bavi izražajem IMP3 proteina kod SCC grkljana.
Cilj istraživanja: Utvrditi međusobnu povezanost izražaja IMP3 s histopatološkim i kliničkim značajkama SCC i prekanceroznih lezija grkljana, što bi omogućilo primjenu IMP3 kao jednog od prognostičkih biobiljega u kancerogenezi skvamoznog epitela grkljana s mogućnostima ciljane terapije.
Metode: Ovo retrospektivno istraživanje obuhvatilo je 153 pacijenta podijeljenih u tri skupine - 68 u skupni SCC, 41 u skupini prekanceroza i 44 u kontrolnoj skupini. Tehnologija tkivnih mikropostrojbi korištena je za imunohistokemijska bojenja uzoraka tkiva u svrhu utvrđivanja izražaja biobiljega IMP3, Ki-67,p53 i ciklin d1.
Rezultati: Utvrdili smo povezanost izražaja IMP3 s histopatološkim i kliničkim značajkama SCC i prekanceroza grkljana. Svi analizirani biomarkeri pokazuju dobru prediktivnu vrijednost (AUC˃0,6). IMP3 je jedini statistički značajan biobiljeg u predikciji ima li ispitanik SCC grkljana ili ne. Ispitanik s IMP3%>12,5 ima 1,1 puta veću vjerojatnost da će imati SCC od ispitanika s IMP3%≤12,5. Obrazac učestalosti izražaja KI-67, a još više IMP3, između tri ispitivane skupine, izgleda tako da su kontrolna skupina i skupina prekanceroza slične, a skupina SCC se od njih značajno razlikuje. Nasuprot tome, kod analize učestalosti izražaja p53 i ciklina D1 nismo naišli na takvo ''grupiranje''.
Zaključak: Oštar skok učestalosti izražaja između skupina prekanceroze i SCC posebno je naglašen kod IMP3. Time on postaje poželjna i važna dijagnostička meta, može utjecati na kliničku odluku da li postoji potreba za dodatnim modalitetima terapije nakon kirurške, a može imati i značajnu prognostičku vrijednost. Preduvjet za to su, naravno, dodatne studije kako bismo rasvijetlili točne molekularne mehanizme koji stoje iza tih molekularno-fenotipskih transformacija stanica prekanceroza na putu nastanka invazivnog SCC grkljana.
Abstract (english) Introduction: Squamous cell carcinoma (SCC) of the larynx represents more than 95% of malignant tumours of the larynx. IMP3 is an oncofetal RNA-binding protein, which, as a biomarker, is associated with the progression of numerous malignant tumours and is useful for the staging of dysplastic lesions.By review of the available scientific literature, we found that there is only one scientific paper that deals with the expression of IMP3 protein in laryngeal SCC.
Aim: To determine the correlation of IMP3 expression with histopathological and clinical features of SCC and precancerous lesions of the larynx, which would allow the use of IMP3 as one of the prognostic biomarkers in carcinogenesis of squamous epithelium of the larynx, with the possibilities of targeted therapy.
Methods: This retrospective study included 153 patients divided into three groups - 68 in the SCC group, 41 in the precancerous group and 44 in the control group. Tissue microarray technology was used for immunohistochemical staining of tissue samples to determine the expression of biomarkers IMP3, Ki-67, p53 and cyclin d1.
Results: We found an association of IMP3 expression with histopathological and clinical features of SCC and laryngeal precancerous lesions. All analysed biomarkers show good predictive value (AUC˃0.6). IMP3 is the only statistically significant biomarker in predicting whether a subject has SCC of the larynx or not. A subject with IMP3%> 12.5 is 1.1 times more likely to have SCC than a subject with IMP3% ≤12.5. The pattern of Ki-67 expression, and even more so IMP3, between the three examined groups, appears to be that the control group and the precancerous group are similar, and the SCC group differs significantly from them. In contrast, we did not find such a "grouping" in the analysis of the frequency of expression of p53 and cyclin D1.
Conclusion: A sharp increase in the frequency of expression between the precancerous and SCC groups is particularly pronounced in IMP3. Thus, it becomes a desirable and important diagnostic target, it can influence the clinical decision whether there is a need for additional modalities of therapy after surgery, and it can also have significant prognostic value. A prerequisite for this are, of course, additional studies to elucidate the exact molecular mechanisms behind these molecular-phenotypic transformations of precancerous cells in the pathway of invasive laryngeal SCC.
Keywords
Biobiljezi
protein IMP3
grkljan
karcinom
prekancerozne lezije.
Keywords (english)
Biomarkers
carcinoma
IMP3 protein
larynx
precancerous lesions
Language croatian
URN:NBN urn:nbn:hr:184:739842
Promotion 2021
Study programme Title: Biomedicine Postgraduate (doctoral) study programme Study programme type: university Study level: postgraduate Academic / professional title: doktor/doktorica znanosti, područje biomedicine i zdravstvo (doktor/doktorica znanosti, područje biomedicine i zdravstvo)
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Created on 2021-03-03 00:29:30