Prognostička vrijednost tkivnog proteomskog profila u stadijima I i II malignoga melanoma kože glave i vrata [Prognostic significance of proteomic profiling applied to stages I and II cutaneous malignant melanoma of the head and neck in stages I and II]

Košec, Andro (2017) Prognostička vrijednost tkivnog proteomskog profila u stadijima I i II malignoga melanoma kože glave i vrata [Prognostic significance of proteomic profiling applied to stages I and II cutaneous malignant melanoma of the head and neck in stages I and II]. PhD thesis, Sveučilište u Zagrebu.

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Abstract

Morphohistopathological parameters are the basis for malignant melanoma classification and prognosis. An increasing number of molecular biomarkers offers new potential for refining diagnostic and prognostic disease categories. However, early stage disease prognosis is only partially defined by morphological and histopathological parameters (primary tumor localization, patient age and gender, mitotic rate, lesion thickness and presence of ulceration). This study is based on proteomic profiling of 31 early stage head and neck cutaneus malignant melanoma tissue samples and six pooled benign pigmented nevi tissue, as a control sample. After identifying the global melanoma proteomic profile, expression of individual proteins was correlated with established prognostic factors and patient survival by recursive partitioning. Relations between individual protein expression levels and disease specific survival were analyzed. Analysis revealed, previously unreported proteins, identified as possible prognostic biomarkers. These are: heterogeneous nuclear ribonucleoprotein M, heat shock protein 90 alpha, profilin-1, tubulin - beta chain, annexin-5 and ribosomal protein L7. Heterogeneous nuclear ribonucleoprotein M was identifed as the principal prognostic factor in our data set. It was shown as independent in relation to other prognostic factors, statistically significant and clinically relevant due to an exceedingly high hazard ratio. These findings add a new dimension in relation to novel melanoma biomarkers, especially in for early disease stages.

Abstract in Croatian

Morfološka i histopatološka obilježja su osnova klasifikacije i prognoze melanoma. Rastući broj molekularnih biljega predstavlja potencijal za unapređenje dijagnostičkih metoda i prognostičkih kategorija bolesti. Prognoza melanoma u ranoj fazi je tek djelomično objašnjena morfohistopatološkim parametrima kao što su lokalizacija primarnog tumora, dob i spol oboljelog, broj mitoza po mm2, debljina tumora i prisustvo ulceracije. Analizirani su profili proteoma 31 melanoma kože glave i vrata u ranom stadiju i šest objedinjenih benignih pigmentiranih nevusa kože kao jednim uzorkom kontrolne skupine. Na temelju profila proteoma melanoma, rekurzivnim particioniranjem je analizirana izraženost proteina s vremenskim razdobljem proteklim od datuma postavljanja dijagnoze do datuma smrti uzrokovane melanomom, (engl. disease specific survival). Ovim su istraživanjem identificirani novi potencijalni biljezi melanoma koji su povezani s prognozom bolesti; heterogeni nuklearni ribonukleoprotein M, heat shock protein 90 alpha, profilin-1, tubulin, beta lanac, aneksin-5 i ribosomski protein L7. Vrijednost izraženosti heterogenog nuklearnog ribonukleoproteina M je glavni prognostički čimbenik u ispitivanom skupu podataka. Neovisan je o svim ostalim ispitivanim prognostičkim čimbenicima, statistički je značajan, i ima klinički značaj zbog velike razlike u omjeru hazarda. Rezultati ove disertacije proširili su spoznaje o postojećim i novootkrivenim proteina u melanomima koji su u ranim stadijima, a pružili su i su i solidan temelj za daljnja a istraživanja prognostičke vrijednosti ovih proteina.

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