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Immunoprofiles and DNA Methylation of Inflammatory Marker Genes in Ulcerative Colitis-Associated Colorectal Tumorigenesis

Immunological and epigenetic changes are interconnected and contribute to tumorigenesis. We determined the immunoprofiles and promoter methylation of inflammation-related genes for colitis-associated colorectal carcinomas (CA-CRC). The results were compared with Lynch syndrome (LS)-associated colore...

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Autores principales: Mäki-Nevala, Satu, Ukwattage, Sanjeevi, Wirta, Erkki-Ville, Ahtiainen, Maarit, Ristimäki, Ari, Seppälä, Toni T., Lepistö, Anna, Mecklin, Jukka-Pekka, Peltomäki, Päivi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8533626/
https://www.ncbi.nlm.nih.gov/pubmed/34680073
http://dx.doi.org/10.3390/biom11101440
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author Mäki-Nevala, Satu
Ukwattage, Sanjeevi
Wirta, Erkki-Ville
Ahtiainen, Maarit
Ristimäki, Ari
Seppälä, Toni T.
Lepistö, Anna
Mecklin, Jukka-Pekka
Peltomäki, Päivi
author_facet Mäki-Nevala, Satu
Ukwattage, Sanjeevi
Wirta, Erkki-Ville
Ahtiainen, Maarit
Ristimäki, Ari
Seppälä, Toni T.
Lepistö, Anna
Mecklin, Jukka-Pekka
Peltomäki, Päivi
author_sort Mäki-Nevala, Satu
collection PubMed
description Immunological and epigenetic changes are interconnected and contribute to tumorigenesis. We determined the immunoprofiles and promoter methylation of inflammation-related genes for colitis-associated colorectal carcinomas (CA-CRC). The results were compared with Lynch syndrome (LS)-associated colorectal tumors, which are characterized by an active immune environment through inherited mismatch repair defects. CA-CRCs (n = 31) were immunohistochemically evaluated for immune cell scores (ICSs) and PDCD1 and CD274 expression. Seven inflammation-associated genes (CD274, NTSR1, PPARG, PTGS2, PYCARD, SOCS1, and SOCS2), the repair gene MGMT, and eight standard marker genes for the CpG Island Methylator Phenotype (CIMP) were investigated for promoter methylation in CA-CRCs, LS tumors (n = 29), and paired normal mucosae by multiplex ligation-dependent probe amplification. All but one CA-CRCs were microsatellite-stable and all LS tumors were microsatellite-unstable. Most CA-CRCs had a high ICS (55%) and a positive CD274 expression in immune cells (52%). NTSR1 revealed frequent tumor-specific hypermethylation in CA-CRC and LS. When compared to LS mucosae, normal mucosae from patients with CA-CRC showed significantly higher methylation of NTSR1 and most CIMP markers. In conclusion, CA-CRCs share a frequent ICS(high)/CD274(pos) expression pattern with LS tumors. Elevated methylation in normal mucosa may indicate field cancerization as a feature of CA-CRC-associated tumorigenesis.
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spelling pubmed-85336262021-10-23 Immunoprofiles and DNA Methylation of Inflammatory Marker Genes in Ulcerative Colitis-Associated Colorectal Tumorigenesis Mäki-Nevala, Satu Ukwattage, Sanjeevi Wirta, Erkki-Ville Ahtiainen, Maarit Ristimäki, Ari Seppälä, Toni T. Lepistö, Anna Mecklin, Jukka-Pekka Peltomäki, Päivi Biomolecules Article Immunological and epigenetic changes are interconnected and contribute to tumorigenesis. We determined the immunoprofiles and promoter methylation of inflammation-related genes for colitis-associated colorectal carcinomas (CA-CRC). The results were compared with Lynch syndrome (LS)-associated colorectal tumors, which are characterized by an active immune environment through inherited mismatch repair defects. CA-CRCs (n = 31) were immunohistochemically evaluated for immune cell scores (ICSs) and PDCD1 and CD274 expression. Seven inflammation-associated genes (CD274, NTSR1, PPARG, PTGS2, PYCARD, SOCS1, and SOCS2), the repair gene MGMT, and eight standard marker genes for the CpG Island Methylator Phenotype (CIMP) were investigated for promoter methylation in CA-CRCs, LS tumors (n = 29), and paired normal mucosae by multiplex ligation-dependent probe amplification. All but one CA-CRCs were microsatellite-stable and all LS tumors were microsatellite-unstable. Most CA-CRCs had a high ICS (55%) and a positive CD274 expression in immune cells (52%). NTSR1 revealed frequent tumor-specific hypermethylation in CA-CRC and LS. When compared to LS mucosae, normal mucosae from patients with CA-CRC showed significantly higher methylation of NTSR1 and most CIMP markers. In conclusion, CA-CRCs share a frequent ICS(high)/CD274(pos) expression pattern with LS tumors. Elevated methylation in normal mucosa may indicate field cancerization as a feature of CA-CRC-associated tumorigenesis. MDPI 2021-09-30 /pmc/articles/PMC8533626/ /pubmed/34680073 http://dx.doi.org/10.3390/biom11101440 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Mäki-Nevala, Satu
Ukwattage, Sanjeevi
Wirta, Erkki-Ville
Ahtiainen, Maarit
Ristimäki, Ari
Seppälä, Toni T.
Lepistö, Anna
Mecklin, Jukka-Pekka
Peltomäki, Päivi
Immunoprofiles and DNA Methylation of Inflammatory Marker Genes in Ulcerative Colitis-Associated Colorectal Tumorigenesis
title Immunoprofiles and DNA Methylation of Inflammatory Marker Genes in Ulcerative Colitis-Associated Colorectal Tumorigenesis
title_full Immunoprofiles and DNA Methylation of Inflammatory Marker Genes in Ulcerative Colitis-Associated Colorectal Tumorigenesis
title_fullStr Immunoprofiles and DNA Methylation of Inflammatory Marker Genes in Ulcerative Colitis-Associated Colorectal Tumorigenesis
title_full_unstemmed Immunoprofiles and DNA Methylation of Inflammatory Marker Genes in Ulcerative Colitis-Associated Colorectal Tumorigenesis
title_short Immunoprofiles and DNA Methylation of Inflammatory Marker Genes in Ulcerative Colitis-Associated Colorectal Tumorigenesis
title_sort immunoprofiles and dna methylation of inflammatory marker genes in ulcerative colitis-associated colorectal tumorigenesis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8533626/
https://www.ncbi.nlm.nih.gov/pubmed/34680073
http://dx.doi.org/10.3390/biom11101440
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