Fibroblasts promoting and restaining malignancy in colorectal cancer

Colorectal cancer, i.e., cancer of the colon and rectum, contributes to circa 10% of new cancer cases and cancer-related deaths. Tumour microenvironment is made of neoplastic cells and a supporting structure termed stroma. One of the stromal cell types is cancer-associated fibroblasts (CAFs), that...

Full description

Bibliographic Details
Main Author: Saari, Maiju
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: 2025
Subjects:
Online Access: https://jyx.jyu.fi/handle/123456789/102035
_version_ 1834856794037420032
author Saari, Maiju
author2 Matemaattis-luonnontieteellinen tiedekunta Faculty of Sciences Bio- ja ympäristötieteiden laitos Department of Biological and Environmental Science Jyväskylän yliopisto University of Jyväskylä
author_facet Saari, Maiju Matemaattis-luonnontieteellinen tiedekunta Faculty of Sciences Bio- ja ympäristötieteiden laitos Department of Biological and Environmental Science Jyväskylän yliopisto University of Jyväskylä Saari, Maiju Matemaattis-luonnontieteellinen tiedekunta Faculty of Sciences Bio- ja ympäristötieteiden laitos Department of Biological and Environmental Science Jyväskylän yliopisto University of Jyväskylä
author_sort Saari, Maiju
datasource_str_mv jyx
description Colorectal cancer, i.e., cancer of the colon and rectum, contributes to circa 10% of new cancer cases and cancer-related deaths. Tumour microenvironment is made of neoplastic cells and a supporting structure termed stroma. One of the stromal cell types is cancer-associated fibroblasts (CAFs), that have been proven to both promote tumour progression in colorectal cancer and possess tumour restraining qualities. The aim of this study was to define prognostic significance of CAFs in colorectal cancer. Based on the expression of selected CAF antibodies and the survival of the patients, CAFs were classified as cancer-restraining and cancer-promoting. We also aimed to define whether the number of cancer-associated fibroblasts associated with strong immune response or colorectal cancer subgroups, DNA mismatch repair (MMR) deficient and proficient. Tissue microarray sections of primary colorectal cancer tumours were immunostained with a selection of cancer-associated fibroblast marker antibodies using multiplex-immunohistochemistry technique. After digitalisation, the sample images were converted to pseudofluorescence images and analysed using a machine learning-based image analysis software QuPath. Detected cells were phenotyped based on the intensity of expressed markers, and tumour and stromal tissues were separated. The prognostic significance of CAF subsets was analysed using Kaplan-Meier survival estimate, Cox regression model and crosstabulation. The results indicated that large number of fibroblasts in colorectal cancer tumour associates with worse survival. This association was seen in colorectal cancer subtype MMR proficient, but not in MMR deficient. High portion of CAFs expressing MCAM and PDPN associated with better survival. The obtained results indicate that cancer-associated fibroblasts may have potential as a prognostic parameter in colorectal cancer, although more research is needed.
first_indexed 2025-05-15T20:01:06Z
format Pro gradu
fullrecord [{"key": "dc.contributor.advisor", "value": "Ahtiainen, Maarit", "language": null, "element": "contributor", "qualifier": "advisor", "schema": "dc"}, {"key": "dc.contributor.advisor", "value": "Tahkola, Ky\u00f6sti", "language": null, "element": "contributor", "qualifier": "advisor", "schema": "dc"}, {"key": "dc.contributor.advisor", "value": "Yl\u00e4nne, Jari", "language": null, "element": "contributor", "qualifier": "advisor", "schema": "dc"}, {"key": "dc.contributor.author", "value": "Saari, Maiju", "language": null, "element": "contributor", "qualifier": "author", "schema": "dc"}, {"key": "dc.date.accessioned", "value": "2025-05-15T11:32:46Z", "language": null, "element": "date", "qualifier": "accessioned", "schema": "dc"}, {"key": "dc.date.available", "value": "2025-05-15T11:32:46Z", "language": null, "element": "date", "qualifier": "available", "schema": "dc"}, {"key": "dc.date.issued", "value": "2025", "language": null, "element": "date", "qualifier": "issued", "schema": "dc"}, {"key": "dc.identifier.uri", "value": "https://jyx.jyu.fi/handle/123456789/102035", "language": null, "element": "identifier", "qualifier": "uri", "schema": "dc"}, {"key": "dc.description.abstract", "value": "", "language": "fi", "element": "description", "qualifier": "abstract", "schema": "dc"}, {"key": "dc.description.abstract", "value": "Colorectal cancer, i.e., cancer of the colon and rectum, contributes to circa 10% of new cancer cases and cancer-related deaths. Tumour microenvironment is made of neoplastic cells and a supporting structure termed stroma. One of the stromal cell types is cancer-associated fibroblasts (CAFs), that have been proven to both promote tumour progression in colorectal cancer and possess tumour restraining qualities. The aim of this study was to define prognostic significance of CAFs in colorectal cancer. Based on the expression of selected CAF antibodies and the survival of the patients, CAFs were classified as cancer-restraining and cancer-promoting. We also aimed to define whether the number of cancer-associated fibroblasts associated with strong immune response or colorectal cancer subgroups, DNA mismatch repair (MMR) deficient and proficient. Tissue microarray sections of primary colorectal cancer tumours were immunostained with a selection of cancer-associated fibroblast marker antibodies using multiplex-immunohistochemistry technique. After digitalisation, the sample images were converted to pseudofluorescence images and analysed using a machine learning-based image analysis software QuPath. Detected cells were phenotyped based on the intensity of expressed markers, and tumour and stromal tissues were separated. The prognostic significance of CAF subsets was analysed using Kaplan-Meier survival estimate, Cox regression model and crosstabulation. The results indicated that large number of fibroblasts in colorectal cancer tumour associates with worse survival. This association was seen in colorectal cancer subtype MMR proficient, but not in MMR deficient. High portion of CAFs expressing MCAM and PDPN associated with better survival. The obtained results indicate that cancer-associated fibroblasts may have potential as a prognostic parameter in colorectal cancer, although more research is needed.", "language": "en", "element": "description", "qualifier": "abstract", "schema": "dc"}, {"key": "dc.description.provenance", "value": "Submitted by Paivi Vuorio (paelvuor@jyu.fi) on 2025-05-15T11:32:46Z\nNo. of bitstreams: 0", "language": "en", "element": "description", "qualifier": "provenance", "schema": "dc"}, {"key": "dc.description.provenance", "value": "Made available in DSpace on 2025-05-15T11:32:46Z (GMT). No. of bitstreams: 0\n Previous issue date: 2025", "language": "en", "element": "description", "qualifier": "provenance", "schema": "dc"}, {"key": "dc.format.extent", "value": "63", "language": null, "element": "format", "qualifier": "extent", "schema": "dc"}, {"key": "dc.language.iso", "value": "eng", "language": null, "element": "language", "qualifier": "iso", "schema": "dc"}, {"key": "dc.rights", "value": "In Copyright", "language": null, "element": "rights", "qualifier": null, "schema": "dc"}, {"key": "dc.subject.other", "value": "cancer-associated fibroblasts", "language": null, "element": "subject", "qualifier": "other", "schema": "dc"}, {"key": "dc.subject.other", "value": "multiplex-immunohistochemistry", "language": null, "element": "subject", "qualifier": "other", "schema": "dc"}, {"key": "dc.subject.other", "value": "tumour microenvironment", "language": null, "element": "subject", "qualifier": "other", "schema": "dc"}, {"key": "dc.title", "value": "Fibroblasts promoting and restaining malignancy in colorectal cancer", "language": null, "element": "title", "qualifier": null, "schema": "dc"}, {"key": "dc.type", "value": "master thesis", "language": null, "element": "type", "qualifier": null, "schema": "dc"}, {"key": "dc.identifier.urn", "value": "URN:NBN:fi:jyu-202505154278", "language": null, "element": "identifier", "qualifier": "urn", "schema": "dc"}, {"key": "dc.contributor.faculty", "value": "Matemaattis-luonnontieteellinen tiedekunta", "language": "fi", "element": "contributor", "qualifier": "faculty", "schema": "dc"}, {"key": "dc.contributor.faculty", "value": "Faculty of Sciences", "language": "en", "element": "contributor", "qualifier": "faculty", "schema": "dc"}, {"key": "dc.contributor.department", "value": "Bio- ja ymp\u00e4rist\u00f6tieteiden laitos", "language": "fi", "element": "contributor", "qualifier": "department", "schema": "dc"}, {"key": "dc.contributor.department", "value": "Department of Biological and Environmental Science", "language": "en", "element": "contributor", "qualifier": "department", "schema": "dc"}, {"key": "dc.contributor.organization", "value": "Jyv\u00e4skyl\u00e4n yliopisto", "language": null, "element": "contributor", "qualifier": "organization", "schema": "dc"}, {"key": "dc.contributor.organization", "value": "University of Jyv\u00e4skyl\u00e4", "language": null, "element": "contributor", "qualifier": "organization", "schema": "dc"}, {"key": "dc.subject.discipline", "value": "Solu- ja molekyylibiologia", "language": "fi", "element": "subject", "qualifier": "discipline", "schema": "dc"}, {"key": "dc.subject.discipline", "value": "Cell and molecular biology", "language": "en", "element": "subject", "qualifier": "discipline", "schema": "dc"}, {"key": "dc.type.coar", "value": "http://purl.org/coar/resource_type/c_bdcc", "language": null, "element": "type", "qualifier": "coar", "schema": "dc"}, {"key": "dc.rights.copyright", "value": "\u00a9 The Author(s)", "language": "fi", "element": "rights", "qualifier": "copyright", "schema": "dc"}, {"key": "dc.rights.accesslevel", "value": "restrictedAccess", "language": null, "element": "rights", "qualifier": "accesslevel", "schema": "dc"}, {"key": "dc.type.publication", "value": "masterThesis", "language": null, "element": "type", "qualifier": "publication", "schema": "dc"}, {"key": "dc.subject.yso", "value": "sy\u00f6p\u00e4taudit", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "paksusuolisy\u00f6p\u00e4", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "per\u00e4suolisy\u00f6p\u00e4", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "fibroblastit", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "biomarkkerit", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "immunohistokemia", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.rights.url", "value": "https://rightsstatements.org/page/InC/1.0/", "language": null, "element": "rights", "qualifier": "url", "schema": "dc"}, {"key": "dc.rights.accessrights", "value": "Tekij\u00e4 ei ole antanut lupaa avoimeen julkaisuun, joten aineisto on luettavissa vain Jyv\u00e4skyl\u00e4n yliopiston kirjaston arkistoty\u00f6semalta. Ks. https://kirjasto.jyu.fi/fi/tyoskentelytilat/laitteet-ja-tilat#autotoc-item-autotoc-2", "language": "fi", "element": "rights", "qualifier": "accessrights", "schema": "dc"}, {"key": "dc.rights.accessrights", "value": "The author has not given permission to make the work publicly available electronically. Therefore the material can be read only at the archival workstation at Jyv\u00e4skyl\u00e4 University Library (https://kirjasto.jyu.fi/fi/tyoskentelytilat/laitteet-ja-tilat#autotoc-item-autotoc-2.", "language": "en", "element": "rights", "qualifier": "accessrights", "schema": "dc"}, {"key": "dc.description.accessibilityfeature", "value": "unknown accessibility", "language": "en", "element": "description", "qualifier": "accessibilityfeature", "schema": "dc"}, {"key": "dc.description.accessibilityfeature", "value": "ei tietoa saavutettavuudesta", "language": "fi", "element": "description", "qualifier": "accessibilityfeature", "schema": "dc"}]
id jyx.123456789_102035
language eng
last_indexed 2025-06-10T20:00:44Z
main_date 2025-01-01T00:00:00Z
main_date_str 2025
publishDate 2025
record_format qdc
source_str_mv jyx
spellingShingle Saari, Maiju Fibroblasts promoting and restaining malignancy in colorectal cancer cancer-associated fibroblasts multiplex-immunohistochemistry tumour microenvironment Solu- ja molekyylibiologia Cell and molecular biology syöpätaudit paksusuolisyöpä peräsuolisyöpä fibroblastit biomarkkerit immunohistokemia
title Fibroblasts promoting and restaining malignancy in colorectal cancer
title_full Fibroblasts promoting and restaining malignancy in colorectal cancer
title_fullStr Fibroblasts promoting and restaining malignancy in colorectal cancer Fibroblasts promoting and restaining malignancy in colorectal cancer
title_full_unstemmed Fibroblasts promoting and restaining malignancy in colorectal cancer Fibroblasts promoting and restaining malignancy in colorectal cancer
title_short Fibroblasts promoting and restaining malignancy in colorectal cancer
title_sort fibroblasts promoting and restaining malignancy in colorectal cancer
title_txtP Fibroblasts promoting and restaining malignancy in colorectal cancer
topic cancer-associated fibroblasts multiplex-immunohistochemistry tumour microenvironment Solu- ja molekyylibiologia Cell and molecular biology syöpätaudit paksusuolisyöpä peräsuolisyöpä fibroblastit biomarkkerit immunohistokemia
topic_facet Cell and molecular biology Solu- ja molekyylibiologia biomarkkerit cancer-associated fibroblasts fibroblastit immunohistokemia multiplex-immunohistochemistry paksusuolisyöpä peräsuolisyöpä syöpätaudit tumour microenvironment
url https://jyx.jyu.fi/handle/123456789/102035 http://www.urn.fi/URN:NBN:fi:jyu-202505154278
work_keys_str_mv AT saarimaiju fibroblastspromotingandrestainingmalignancyincolorectalcancer