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

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Mäki-Nevala , S , Ukwattage , S , Wirta , E-V , Ahtiainen , M , Ristimäki , A , Seppälä , T T , Lepistö , A , Mecklin , J-P & Peltomäki , P 2021 , ' Immunoprofiles and DNA Methylation of Inflammatory Marker Genes in Ulcerative Colitis-Associated Colorectal Tumorigenesis ' , Biomolecules , vol. 11 , no. 10 , 1440 . https://doi.org/10.3390/biom11101440

Title: Immunoprofiles and DNA Methylation of Inflammatory Marker Genes in Ulcerative Colitis-Associated Colorectal Tumorigenesis
Author: Mäki-Nevala, Satu; Ukwattage, Sanjeevi; Wirta, Erkki-Ville; Ahtiainen, Maarit; Ristimäki, Ari; Seppälä, Toni T.; Lepistö, Anna; Mecklin, Jukka-Pekka; Peltomäki, Päivi
Contributor organization: Department of Medical and Clinical Genetics
Department of Pathology
HUSLAB
HUS Diagnostic Center
ATG - Applied Tumor Genomics
HUS Abdominal Center
II kirurgian klinikka
Date: 2021-10
Language: eng
Number of pages: 17
Belongs to series: Biomolecules
ISSN: 2218-273X
DOI: https://doi.org/10.3390/biom11101440
URI: http://hdl.handle.net/10138/337332
Abstract: 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 ICShigh/CD274(pos) expression pattern with LS tumors. Elevated methylation in normal mucosa may indicate field cancerization as a feature of CA-CRC-associated tumorigenesis.
Subject: Lynch syndrome
ulcerative colitis
colon cancer
immune cell score
DNA methylation
inflammation-associated genes
CANCERS
EPIGENETICS
INSTABILITY
PHENOTYPE
MUCOSA
1182 Biochemistry, cell and molecular biology
3121 General medicine, internal medicine and other clinical medicine
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion


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