The link between intestinal mucins, the gut microbiota, and colon cancer sidedness

Paksusuolen syöpä voidaan jakaa pääkasvaimen anatomisen sijainnin perusteella oikean- ja vasemmanpuoleiseen paksusuolen syöpään, jotka eroavat toisistaan esimerkiksi tyypillisten riskitekijöiden, oirekuvan sekä kuolleisuuden perusteella. Paksusuolen syöpään liittyy usein erilaisia muutoksia limakalv...

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Main Author: Peltonen, Olivia
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: 2024
Subjects:
Online Access: https://jyx.jyu.fi/handle/123456789/97657
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author Peltonen, Olivia
author2 Matemaattis-luonnontieteellinen tiedekunta Faculty of Sciences Bio- ja ympäristötieteiden laitos Department of Biological and Environmental Science Jyväskylän yliopisto University of Jyväskylä
author_facet Peltonen, Olivia Matemaattis-luonnontieteellinen tiedekunta Faculty of Sciences Bio- ja ympäristötieteiden laitos Department of Biological and Environmental Science Jyväskylän yliopisto University of Jyväskylä Peltonen, Olivia Matemaattis-luonnontieteellinen tiedekunta Faculty of Sciences Bio- ja ympäristötieteiden laitos Department of Biological and Environmental Science Jyväskylän yliopisto University of Jyväskylä
author_sort Peltonen, Olivia
datasource_str_mv jyx
description Paksusuolen syöpä voidaan jakaa pääkasvaimen anatomisen sijainnin perusteella oikean- ja vasemmanpuoleiseen paksusuolen syöpään, jotka eroavat toisistaan esimerkiksi tyypillisten riskitekijöiden, oirekuvan sekä kuolleisuuden perusteella. Paksusuolen syöpään liittyy usein erilaisia muutoksia limakalvojen musiinikerroksessa sekä suolistomikrobiston rakenteessa. Näiden muutosten uskotaan olevan yhteydessä myös paksusuolen syövän puoleisuuseroihin, mutta aiemmissa tutkimuksissa saadut tulokset aiheesta ovat ristiriitaisia. Koska paksusuolen syövän puoleisuuden ja siihen liittyvien kliinisten ominaisuuksien taustalla vaikuttavat monimutkaiset syy-seuraussuhteet ovat vielä epäselviä, olisi tärkeää ymmärtää paremmin syövän syntyyn ja kehitykseen vaikuttavia mikrobiaalisia ja molekulaarisia tekijöitä. Tämän tutkielman tarkoituksena on tuottaa lisää tietoa aiheesta vertaamalla musiinien ekspressiota sekä suolistomikrobiston koostumusta vasemman- ja oikeanpuoleisessa paksusuolen syövässä sekä terveessä paksusuolessa. Tutkimuksessa käytettiin syöpäpotilaiden kasvaimista ja terveestä paksusuolesta kerättyjä kudosnäytteitä, sekä näiltä koehenkilöiltä ja terveiltä kontrollihenkilöiltä kerättyjä ulostenäytteitä. Kudosten ja musiinikerroksen rakennetta tutkittiin immunohistologisen värjäyksen avulla. Musiinien ekspressiota kudoksissa tutkittiin dPCR:n avulla kvantifioimalla neljän tärkeimmän MUC-mRNA:n ekspressiota kudosnäytteissä. Lisäksi kasvaimista ja ulostenäytteistä eristettyä bakteriaalista DNA:ta käytettiin suolistomikrobiston koostumuksen selvittämiseen ryhmissä 16S rRNA-geenisekvensoinnin avulla. Tässä tutkielmassa ei löydetty yhteyttä MUC-ekspression ja paksusuolen syövän tai sen puoleisuuden välillä. Myöskään merkitseviä eroja alfadiversiteetissä ei löytynyt ryhmien välillä. Sen sijaan beetadiversiteetti oli hyvin erilainen syöpäpotilaiden ja verrokkien välillä. Näiden ryhmien, mutta myös oikean- ja vasemmanpuoleisten paksusuolen syöpien suolistomikrobiston väliltä löytyi monia taksonomisia eroavaisuuksia. Tutkielmassa saadut tulokset ovat alustavia, mutta ne osoittavat, että aiheeseen liittyvää jatkotutkimusta suuremmalla otoksella ja monipuolisempia näytteitä verraten tarvitaan. Tietoa paksusuolen syövän puoleisuuseroista voitaisiin tulevaisuudessa käyttää esimerkiksi apuna yksilöllisempien syöpähoitojen ja luotettavampien seulontamenetelmien kehittämisessä sekä paksusuolen syövän ennaltaehkäisyssä. Colon cancer can be divided into right- and left-sided colon cancer based on the anatomical location of the primary tumor. Colon cancer sidedness is linked to differential clinical characteristics such as risk factors, incidence, symptoms, therapy response, and survival. Colon cancer is associated with changes in the mucosal layer, including mucin proteins, and the gut microbiota. The relationship between colon cancer sidedness and the changes in mucins as well as the gut microbiota composition remains unclear. Because of the previously established association between primary tumor location and many clinical characteristics of colon cancer, understanding the microbial and molecular background of colon cancer development is very important. This thesis aims to obtain more information on the subject by comparing mucin expression and the gut microbiota composition in left- and right-sided colon cancers and healthy colon. Tissue samples from tumors and normal adjacent colon from subjects with right- and left-sided colon cancer, and faecal samples from these subjects as well as healthy control subjects were used in this thesis. Immunohistochemistry was used to observe the differences in the tissues and their mucosal layer in groups. The expression of four most relevant MUC mRNAs in the tissue samples was quantified using dPCR to compare the mucin expression between the groups. Tumors and faecal samples were then used to isolate and amplify the bacterial DNA in 16S rRNA gene sequencing to compare the gut microbiota composition between the groups. In this thesis, no statistically significant differences in MUC expression were found between the colon cancer and normal adjacent tissue, or between right- and left-sided colon cancer. Alpha diversity also didn’t differ between groups. However, beta diversity was significantly different in the faecal samples from colon cancer patients and the healthy controls. Multiple taxonomical differences were also found between these groups, as well as the right- and left-sided colon cancer groups. Ultimately, the preliminary results obtained in this thesis suggest that further research using a larger sample size, and comprehensive samples is needed. In the future, information on the relationship between mucins, the gut microbiota and colon cancer sidedness could potentially be used in the development of more individualized treatments, and more reliable screening for colon cancer, and to efficiently prevent the formation of colon cancer.
first_indexed 2024-10-24T20:01:36Z
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spellingShingle Peltonen, Olivia The link between intestinal mucins, the gut microbiota, and colon cancer sidedness MUC1 MUC2 MUC5AC MUC6 mucous membranes Solu- ja molekyylibiologia Cell and molecular biology 4013 syöpätaudit paksusuolisyöpä suoliston taudit suolisto suolistosyövät mikrobisto paksusuoli mikrobit suolistomikrobisto cancerous diseases cancer of the large intestine intestinal diseases intestines bowel cancer microbiome large intestine microbes gastrointestinal microbiota
title The link between intestinal mucins, the gut microbiota, and colon cancer sidedness
title_full The link between intestinal mucins, the gut microbiota, and colon cancer sidedness
title_fullStr The link between intestinal mucins, the gut microbiota, and colon cancer sidedness The link between intestinal mucins, the gut microbiota, and colon cancer sidedness
title_full_unstemmed The link between intestinal mucins, the gut microbiota, and colon cancer sidedness The link between intestinal mucins, the gut microbiota, and colon cancer sidedness
title_short The link between intestinal mucins, the gut microbiota, and colon cancer sidedness
title_sort link between intestinal mucins the gut microbiota and colon cancer sidedness
title_txtP The link between intestinal mucins, the gut microbiota, and colon cancer sidedness
topic MUC1 MUC2 MUC5AC MUC6 mucous membranes Solu- ja molekyylibiologia Cell and molecular biology 4013 syöpätaudit paksusuolisyöpä suoliston taudit suolisto suolistosyövät mikrobisto paksusuoli mikrobit suolistomikrobisto cancerous diseases cancer of the large intestine intestinal diseases intestines bowel cancer microbiome large intestine microbes gastrointestinal microbiota
topic_facet 4013 Cell and molecular biology MUC1 MUC2 MUC5AC MUC6 Solu- ja molekyylibiologia bowel cancer cancer of the large intestine cancerous diseases gastrointestinal microbiota intestinal diseases intestines large intestine microbes microbiome mikrobisto mikrobit mucous membranes paksusuoli paksusuolisyöpä suolisto suolistomikrobisto suoliston taudit suolistosyövät syöpätaudit
url https://jyx.jyu.fi/handle/123456789/97657 http://www.urn.fi/URN:NBN:fi:jyu-202410246514
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