RNA sequencing and immunohistochemistry as tools to identify new biomarkers for pulmonary carcinoid tumor patients

Syövän kehittymisessä tietyt geenit ovat usein yliekspressoituja ja niiden tunnistaminen tarjoaa mahdollisuuksia löytää diagnostisia, prediktiivisiä ja prognostisia merkkiaineita sekä kohteita syöpätautien lääkehoidoille. Tässä tutkimuksessa RNA-sekvensoinnin ja immunohistokemian avulla pyrittiin tu...

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Main Author: Niinimäki, Jenni
Other Authors: Matemaattis-luonnontieteellinen tiedekunta, Faculty of Sciences, Bio- ja ympäristötieteiden laitos, Department of Biological and Environmental Science, Jyväskylän yliopisto, University of Jyväskylä
Format: Master's thesis
Language:eng
Published: 2021
Subjects:
Online Access: https://jyx.jyu.fi/handle/123456789/76923
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author Niinimäki, Jenni
author2 Matemaattis-luonnontieteellinen tiedekunta Faculty of Sciences Bio- ja ympäristötieteiden laitos Department of Biological and Environmental Science Jyväskylän yliopisto University of Jyväskylä
author_facet Niinimäki, Jenni Matemaattis-luonnontieteellinen tiedekunta Faculty of Sciences Bio- ja ympäristötieteiden laitos Department of Biological and Environmental Science Jyväskylän yliopisto University of Jyväskylä Niinimäki, Jenni Matemaattis-luonnontieteellinen tiedekunta Faculty of Sciences Bio- ja ympäristötieteiden laitos Department of Biological and Environmental Science Jyväskylän yliopisto University of Jyväskylä
author_sort Niinimäki, Jenni
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description Syövän kehittymisessä tietyt geenit ovat usein yliekspressoituja ja niiden tunnistaminen tarjoaa mahdollisuuksia löytää diagnostisia, prediktiivisiä ja prognostisia merkkiaineita sekä kohteita syöpätautien lääkehoidoille. Tässä tutkimuksessa RNA-sekvensoinnin ja immunohistokemian avulla pyrittiin tunnistamaan uusia merkkiaineita keuhkon karsinoidikasvaimista. Tutkimusaineisto koostui 128:n Helsingin yliopistollisen sairaalan karsinoidikasvainpotilaan (PC) diagnostisista formaliinifiksoiduista, parafiiniin valetuista kasvainnäytteistä vuosilta 1990–2013. Geeniekspressiota tutkittaessa HSP90AB1 osoitti voimakasta ilmentymistä metastasoineiden PC-kasvainten ryhmässä (p = 0.002). Myös geenin paralogi, HSP90AA1, ekspressoitui normaalia voimakkaammin. Arvioitaessa immunohistokemiallisin värjäyksin näiden geenien koodaamien proteiinien ekspressiotasojen suhdetta erilaisiin kliinispatologisiin muuttujiin, havaittiin korkean Hsp90-α ja -β ekspression assosioituvan potilaan huonontuneeseen ennusteeseen (p = 0.009) sekä kohonneeseen tautikuoleman riskiin. Johtopäätöksenä, RNA-sekvensointi osoittautui toimivan hyvin geenien ilmentymisen tutkimiseen formaliinifiksoiduista, parafiiniin valetuista PC-kasvainnäytteistä. Menetelmää hyödyntäen kyettiin osoittamaan yhteys kohonneen HSP90AB1-ekspression ja kasvaimen aggressiivisuuden välillä. Immunohistokemialla osoitettavaa sytoplasmista Hsp90-α ja -β ilmentymistä voitaneen jatkossa hyödyntää yksittäisten PC-potilaiden ennusteen arvioinnissa. Hsp90-proteiinin inhibointi voisi olla tulevaisuuden hoitomuoto PC-tautiin. In cancer initiation, development and progress some genes are often overexpressed or altered, providing potential diagnostic, predictive and prognostic markers as well as therapeutic targets for the treatment. In this study, RNA sequencing and immunohistochemistry were used to detect novel biomarkers for pulmonary carcinoid (PC) tumor patients. Altogether, 128 formalin-fixed, paraffin-embedded PC tumor samples from patients who were surgically treated in the Helsinki University Hospital between 1990 and 2013 were included in the study. In gene expression analysis, HSP90AB1 mRNA expression was found to be significantly elevated in the group of metastatic PC tumors (p = 0.002). The paralog of the gene, HSP90AA1, was also somewhat overexpressed. When immunohistochemistry was used to assess the relationship between the expression levels of the proteins encoded by these genes and various clinicopathological factors, increased Hsp90-α and -β expression was found to be associated with poor patient outcome (p = 0.009) and increased risk of disease-specific death. In conclusion, RNA sequencing was found to serve well in gene expression analyzes of formalin-fixed, paraffin-embedded PC tumor samples and the method was able to demonstrate an association between the overexpression of HSP90AB1 and the aggressiveness of the tumor. The immunohistochemical assessment of cytoplasmic Hsp90-α and -β protein expressions could be further utilized to assess the prognosis of individual patients. Based on these findings, inhibition of Hsp90 could become potential treatment target for PC disease.
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spellingShingle Niinimäki, Jenni RNA sequencing and immunohistochemistry as tools to identify new biomarkers for pulmonary carcinoid tumor patients atyyppinen karsinoidi tyypillinen karsinoidi lämpöshokkiproteiini transkriptomi atypical carcinoid typical carcinoid heat-shock protein transcriptome Solu- ja molekyylibiologia Cell and molecular biology 4013 geeniekspressio bioinformatiikka karsinoidit gene expression bioinformatics carcinoids
title RNA sequencing and immunohistochemistry as tools to identify new biomarkers for pulmonary carcinoid tumor patients
title_full RNA sequencing and immunohistochemistry as tools to identify new biomarkers for pulmonary carcinoid tumor patients
title_fullStr RNA sequencing and immunohistochemistry as tools to identify new biomarkers for pulmonary carcinoid tumor patients RNA sequencing and immunohistochemistry as tools to identify new biomarkers for pulmonary carcinoid tumor patients
title_full_unstemmed RNA sequencing and immunohistochemistry as tools to identify new biomarkers for pulmonary carcinoid tumor patients RNA sequencing and immunohistochemistry as tools to identify new biomarkers for pulmonary carcinoid tumor patients
title_short RNA sequencing and immunohistochemistry as tools to identify new biomarkers for pulmonary carcinoid tumor patients
title_sort rna sequencing and immunohistochemistry as tools to identify new biomarkers for pulmonary carcinoid tumor patients
title_txtP RNA sequencing and immunohistochemistry as tools to identify new biomarkers for pulmonary carcinoid tumor patients
topic atyyppinen karsinoidi tyypillinen karsinoidi lämpöshokkiproteiini transkriptomi atypical carcinoid typical carcinoid heat-shock protein transcriptome Solu- ja molekyylibiologia Cell and molecular biology 4013 geeniekspressio bioinformatiikka karsinoidit gene expression bioinformatics carcinoids
topic_facet 4013 Cell and molecular biology Solu- ja molekyylibiologia atypical carcinoid atyyppinen karsinoidi bioinformatics bioinformatiikka carcinoids geeniekspressio gene expression heat-shock protein karsinoidit lämpöshokkiproteiini transcriptome transkriptomi typical carcinoid tyypillinen karsinoidi
url https://jyx.jyu.fi/handle/123456789/76923 http://www.urn.fi/URN:NBN:fi:jyu-202107014111
work_keys_str_mv AT niinimäkijenni rnasequencingandimmunohistochemistryastoolstoidentifynewbiomarkersforpulmonarycar